Pharmacological treatment of constipation in palliative care

aClinic of Palliative Medicine, MediClin Robert Janker Klinik bUniversity Clinic for Palliative Medicine, Rheinische Friedrich-Wilhelms-University, Bonn cDepartment of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Germany.
Current opinion in supportive and palliative care (Impact Factor: 1.66). 03/2013; 7(2). DOI: 10.1097/SPC.0b013e32835f1e17
Source: PubMed


Purpose of review:
The prevalence of constipation in palliative care patients varies. There is uncertainty about the choice from varying recommendations for pharmacological management of constipation and a varying clinical practice in palliative care settings. The purpose of the review was to evaluate the current recommendations of therapy guidelines and to determine the effectiveness and safety of laxative administration for the management of constipation in palliative care patients.

Recent findings:
Despite the clinical importance, there are limited data on the efficacy and safety of laxatives in palliative care patients. The social acceptability varies from country to country, but overall, oral laxatives should, where possible, be used in preference. Systemic opioid antagonists, such as naloxone and methylnaltrexone have been studied in few clinical trials. There is a paucity of well designed, prospective, randomized controlled trials with large enough numbers of patients suffering from constipation and treated with pharmacological methods.

There are limited data available on the conventional pharmacological treatment of constipation in palliative care patients due to insufficient randomized controlled trials. However, subcutaneously administered methylnaltrexone was found to be effective in aiding of laxation and well tolerated with limited or transient side effects in palliative care patients.

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    ABSTRACT: Background: Constipation is a common symptom experienced during pregnancy. It has a range of consequences from reduced quality of life and perception of physical health to haemorrhoids. An understanding of the effectiveness and safety of treatments for constipation in pregnancy is important for the clinician managing pregnant women. Objectives: To assess the effectiveness and safety of interventions (pharmacological and non-pharmacological) for treating constipation in pregnancy. Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2015), and the WHO International Clinical Trials Registry Platform (ICTRP) (30 April 2015) and reference lists of retrieved studies. Selection criteria: We considered all published, unpublished and ongoing randomised controlled trials (RCTs), cluster-RCTs and quasi-RCTs, evaluating interventions (pharmacological and non-pharmacological) for constipation in pregnancy. Cross-over studies were not eligible for inclusion in this review. Trials published in abstract form only (without full text publication) were not eligible for inclusion.We compared one intervention (pharmacological or non-pharmacological) against another intervention, placebo or no treatment. Data collection and analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Main results: Four studies were included, but only two studies with a total of 180 women contributed data to this review. It was not clear whether they were RCTs or quasi-RCTs because the sequence generation was unclear. We classified the overall risk of bias of three studies as moderate and one study as high risk of bias. No meta-analyses were carried out due to insufficient data.There were no cluster-RCTs identified for inclusion. Comparisons were available for stimulant laxatives versus bulk-forming laxatives, and fibre supplementation versus no intervention. There were no data available for any other comparisons.During the review process we found that studies reported changes in symptoms in different ways. To capture all data available, we added a new primary outcome (improvement in constipation) - this new outcome was not prespecified in our published protocol. Stimulant laxatives versus bulk-forming laxativesNo data were identified for any of this review's prespecified primary outcomes: pain on defecation, frequency of stools and consistency of stools.Compared to bulk-forming laxatives, pregnant women who received stimulant laxatives had significantly more improvement in constipation (risk ratio (RR) 1.59, 95% confidence interval (CI) 1.21 to 2.09; 140 women, one study, moderate quality of evidence), but also significantly more abdominal discomfort (RR 2.33, 95% CI 1.15 to 4.73; 140 women, one study, low quality of evidence), and borderline difference in diarrhoea (RR 4.50, 95% CI 1.01 to 20.09; 140 women, one study, moderate quality of evidence). In addition, there was no significant difference in women's satisfaction (RR 1.06, 95% CI 0.77 to 1.46; 140 women, one study, moderate quality of evidence).No usable data were identified for any of this review's secondary outcomes: quality of life; dehydration; electrolyte imbalance; acute allergic reaction; or asthma. Fibre supplementation versus no interventionPregnant women who received fibre supplementation had significantly higher frequency of stools compared to no intervention (mean difference (MD) 2.24 times per week, 95% CI 0.96 to 3.52; 40 women, one study, moderate quality of evidence). Fibre supplementation was associated with improved stool consistency as defined by trialists (hard stool decreased by 11% to 14%, normal stool increased by 5% to 10%, and loose stool increased by 0% to 6%).No usable data were reported for either the primary outcomes of pain on defecation and improvement in constipation or any of this review's secondary outcomes as listed above. Quality Five outcomes were assessed with the GRADE software: improvement in constipation, frequency of stools, abdominal discomfort, diarrhoea and women's satisfaction. These were assessed to be of moderate quality except for abdominal discomfort which was assessed to be of low quality. The results should therefore be interpreted with caution. There were no data available for evaluation of pain on defecation or consistency of stools. Authors' conclusions: There is insufficient evidence to comprehensively assess the effectiveness and safety of interventions (pharmacological and non-pharmacological) for treating constipation in pregnancy, due to limited data (few studies with small sample size and no meta-analyses). Compared with bulk-forming laxatives, stimulant laxatives appear to be more effective in improvement of constipation (moderate quality evidence), but are accompanied by an increase in diarrhoea (moderate quality evidence) and abdominal discomfort (low quality evidence) and no difference in women's satisfaction (moderate quality evidence). Additionally, fibre supplementation may increase frequency of stools compared with no intervention (moderate quality evidence), although these results were of moderate risk of bias.There were no data for a comparison of other types of interventions, such as osmotic laxatives, stool softeners, lubricant laxatives and enemas and suppositories.More RCTs evaluating interventions for treating constipation in pregnancy are needed. These should cover different settings and evaluate the effectiveness of various interventions (including fibre, osmotic, and stimulant laxatives) on improvement in constipation, pain on defecation, frequency of stools and consistency of stools.
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