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Cochrane Database of Systematic Reviews

Mu‐opioid antagonists for opioid‐induced bowel dysfunction in people with cancer and people receiving palliative care

Overview of attention for article published in Cochrane database of systematic reviews, June 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (91st percentile)
  • Above-average Attention Score compared to outputs of the same age and source (58th percentile)

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Mu‐opioid antagonists for opioid‐induced bowel dysfunction in people with cancer and people receiving palliative care
Published in
Cochrane database of systematic reviews, June 2018
DOI 10.1002/14651858.cd006332.pub3
Pubmed ID

Bridget Candy, Louise Jones, Victoria Vickerstaff, Philip J Larkin, Patrick Stone


Opioid-induced bowel dysfunction (OIBD) is characterised by constipation, incomplete evacuation, bloating, and gastric reflux. It is one of the major adverse events of treatment for pain in cancer and in palliative care, resulting in increased morbidity and reduced quality of life.This is an update of two Cochrane reviews. One was published in 2011, Issue 1 on laxatives and methylnaltrexone for the management of constipation in people receiving palliative care; this was updated in 2015 and excluded methylnaltrexone. The other was published in 2008, Issue 4 on mu-opioid antagonists (MOA) for OIBD. In this updated review, we only included trials on MOA (including methylnaltrexone) for OIBD in people with cancer and people receiving palliative care. To assess the effectiveness and safety of MOA for OIBD in people with cancer and people receiving palliative care. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, and Web of Science to August 2017. We also searched clinical trial registries and regulatory websites. We contacted manufacturers of MOA to identify further data. We included randomised controlled trials (RCTs) that assessed the effectiveness and safety of MOA for OIBD in people with cancer and people at a palliative stage irrespective of the type of terminal disease they experienced. Two review authors assessed risk of bias and extracted data. The appropriateness of combining data from the trials depended upon sufficient homogeneity across the trials. Our primary outcomes were laxation, impact on pain relief, and adverse events. Impact on pain relief was a primary outcome because a possible adverse effect of MOAs is a reduction in pain relief from opioids. We assessed the evidence on these outcomes using GRADE. We identified four new trials for this update, bringing the total number included in this review to eight. In total, 1022 men and women with cancer irrespective of stage or at a palliative care stage of any disease were randomised across the trials. The MOAs evaluated were oral naldemedine and naloxone (alone or in combination with oxycodone), and subcutaneous methylnaltrexone. The trials compared with MOA with a placebo or with the active intervention administered at different doses or in combination with other drugs. The trial of naldemedine and the two of naloxone in combination with oxycodone were in people with cancer irrespective of disease stage. The trial on naloxone alone was in people with advanced cancer. The four trials on methylnaltrexone were undertaken in palliative care where most participants had cancer. All trials were vulnerable to biases; four were at a high risk as they involved a sample of fewer than 50 participants per arm.In the trial of naldemedine compared to placebo in 225 participants, there were more spontaneous laxations over the two-week treatment for the intervention group (risk ratio (RR) 1.93, 95% confidence intervals (CI) 1.36 to 2.74; moderate-quality evidence). In comparison with higher doses, lower doses resulted in fewer spontaneous laxations (0.1 mg versus 0.2 mg: RR 0.73, 95% CI 0.55 to 0.95; 0.1 mg versus 0.4 mg: RR 0.69, 95% CI 0.53 to 0.89; moderate-quality evidence). There was moderate-quality evidence that naldemedine had no effect on opiate withdrawal. There were five serious adverse events. All were in people taking naldemedine (low-quality evidence). There was an increase in the occurrence of other (non-serious) adverse events in the naldemedine groups (RR 1.36, 95% CI 1.04 to 1.79, moderate-quality evidence). The most common adverse event was diarrhoea.The trials on naloxone taken either on its own, or in combination with oxycodone (an opioid) compared to oxycodone only did not evaluate laxation response over the first two weeks of administration. There was very low-quality evidence that naloxone alone, and moderate-quality evidence that oxycodone/naloxone, had no effect on analgesia. There was low-quality evidence that oxycodone/naloxone did not increase the risk of serious adverse events and moderate-quality evidence that it did not increase risk of adverse events.In combined analysis of two trials of 287 participants, we found methylnaltrexone compared to placebo induced more laxations within 24 hours (RR 2.77, 95% CI 1.91 to 4.04. I² = 0%; moderate-quality evidence). In combined analysis, we found methylnaltrexone induced more laxation responses over two weeks (RR 9.98, 95% CI 4.96 to 20.09. I² = 0%; moderate-quality evidence). The proportion of participants who had a rescue-free laxation response within 24 hours of the first dose was 59.1% in the methylnaltrexone arms and 19.1% in the placebo arm. There was moderate-quality evidence that the rate of opioid withdrawal was not affected. Methylnaltrexone did not increase the likelihood of a serious adverse event; there were fewer in the intervention arm (RR 0.59, 95% CI 0.38 to 0.93; I² = 0%; moderate-quality evidence). There was no difference in the proportion of participants experiencing an adverse event (RR 1.17, 95% CI 0.94 to 1.45; I² = 74%; low-quality evidence). Methylnaltrexone increased the likelihood of abdominal pain and flatulence.Two trials compared differing methylnaltrexone schedules of higher doses with lower doses. For early laxation, there was low-quality evidence of no clear difference between doses on analgesia and adverse events. Both trials measured laxation response within 24 hours of first dose (trial one: RR 0.82, 95% CI 0.41 to 1.66; trial two: RR 1.07, 95% CI 0.81 to 1.42). In this update, the conclusions for naldemedine are new. There is moderate-quality evidence to suggest that, taken orally, naldemedine improves bowel function over two weeks in people with cancer and OIBD but increases the risk of adverse events. The conclusions on naloxone and methylnaltrexone have not changed. The trials on naloxone did not assess laxation at 24 hours or over two weeks. There is moderate-quality evidence that methylnaltrexone improves bowel function in people receiving palliative care in the short term and over two weeks, and low-quality evidence that it does not increase adverse events. There is a need for more trials including more evaluation of adverse events. None of the current trials evaluated effects in children.

X Demographics

X Demographics

The data shown below were collected from the profiles of 27 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 339 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 339 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 39 12%
Researcher 35 10%
Student > Master 32 9%
Student > Ph. D. Student 24 7%
Student > Doctoral Student 24 7%
Other 65 19%
Unknown 120 35%
Readers by discipline Count As %
Medicine and Dentistry 102 30%
Nursing and Health Professions 43 13%
Psychology 18 5%
Pharmacology, Toxicology and Pharmaceutical Science 12 4%
Social Sciences 7 2%
Other 33 10%
Unknown 124 37%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 27. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 February 2023.
All research outputs
of 25,382,440 outputs
Outputs from Cochrane database of systematic reviews
of 11,485 outputs
Outputs of similar age
of 343,126 outputs
Outputs of similar age from Cochrane database of systematic reviews
of 155 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,485 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 39.9. This one has gotten more attention than average, scoring higher than 72% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 343,126 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 91% of its contemporaries.
We're also able to compare this research output to 155 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 58% of its contemporaries.