Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Dec 22;12(12):CD012619.
doi: 10.1002/14651858.CD012619.pub3.

Interventions for preventing distal intestinal obstruction syndrome (DIOS) in cystic fibrosis

Will Carroll  1 , Jessica Green  2 , Francis J Gilchrist  2
Affiliations
Review

Interventions for preventing distal intestinal obstruction syndrome (DIOS) in cystic fibrosis

Will Carroll et al. Cochrane Database Syst Rev. .

Abstract

Background: Cystic fibrosis (CF) is the most common, life-limiting, genetically inherited disease. It affects multiple organs, particularly the respiratory system. However, gastrointestinal problems such as constipation and distal intestinal obstruction syndrome (DIOS) are also important and well-recognised complications in CF. They share similar symptoms e.g. bloating, abdominal pain, but are distinct conditions. Constipation occurs when there is gradual faecal impaction of the colon, but DIOS occurs when there is an accumulation of faeces and sticky mucus, forming a mass in the distal part of the small intestine. The mass may partially block the intestine (incomplete DIOS) or completely block the intestine (complete DIOS). Symptoms of DIOS can affect quality of life and other aspects of CF health, such as airway clearance, exercise, sleep and nutritional status. Treatment of constipation and prevention of complete bowel obstruction are required for gastrointestinal management in CF. However, many different strategies are used in clinical practice and there is a lack of consensus. The importance of this topic was highlighted in a recent research priority setting exercise by the James Lind Alliance.

Objectives: To evaluate the effectiveness and safety of laxative agents of differing types for preventing DIOS (complete and incomplete) in children and adults with CF.

Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of search: 09 September 2021. We also searched online trial registries. Date of last search: 12 October 2021.

Selection criteria: Randomised and quasi-randomised controlled parallel trials comparing laxative therapy for preventing DIOS (including osmotic agents, stimulants, mucolytics and substances with more than one action) at any dose to placebo, no treatment or an alternative laxative therapy, in people of any age with pancreatic sufficient or insufficient CF and any stage of lung disease. Randomised cross-over trials were judged on an individual basis.

Data collection and analysis: Two authors independently assessed trials for inclusion, extracted outcome data and performed a risk of bias assessment for the included data. We judged the certainty of the evidence using GRADE criteria.

Main results: We included one cross-over trial (17 participants) with a duration of 12 months, in which participants were randomly allocated to either cisapride (a gastro-prokinetic agent) or placebo for six months each. The trial had an unclear risk of bias for most domains but had a high risk of reporting bias. Radiograph scores revealed no difference in occurrence of DIOS between cisapride and placebo (narrative report, no data provided). There were no adverse effects. Symptom scores were the only secondary outcome within the review that were reported. Total gastrointestinal symptom scores favoured cisapride with a statistically significant mean difference (MD) of -7.60 (95% confidence interval (CI) -14.73 to -0.47). There was no significant difference at six months between cisapride and placebo for abdominal distension, MD -0.90 (95% CI -2.39 to 0.59) or abdominal pain, MD -0.4 (95% CI -2.05 to 1.25). The global symptom scores (whether individuals felt better or worse) were reported in the paper to favour cisapride and be statistically significant (P < 0.05). We assessed the available data to be very low certainty. There was a great deal of missing data from the included trial and the investigators failed to report numerical data for many outcomes. The overall risk of bias of the trial was unclear and it had a high risk for reporting bias. There was also indirectness; the trial drug (cisapride) has since been removed from the market in several countries due to adverse effects, thus it has no current applicability for preventing DIOS. The included trial also had very few participants, which downgraded the certainty a further level for precision.

Authors' conclusions: There is an absence of evidence for interventions for the prevention of DIOS. As there was only one included trial, we could not perform a meta-analysis of the data. Furthermore, the included trial compared a prokinetic agent (cisapride) that is no longer licensed for use in a number of countries due to the risk of serious cardiac events, a finding that came to light after the trial was conducted. Therefore, the limited findings from the trial are not applicable in current clinical practice. Overall, a great deal more research needs to be undertaken on gastrointestinal complications in CF, as this is a very poorly studied area compared to respiratory complications in CF.

PubMed Disclaimer

Conflict of interest statement

Jessica Green declares no known potential conflict of interest.

Dr Will Carroll declares no known potential conflict of interest.

Dr Francis J Gilchrist declares no known potential conflict of interest.

Figures

1
1
Study flow diagram (Moher 2009)
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: Cisapride versus placebo, Outcome 1: Total gastrointestinal symptoms
1.2
1.2. Analysis
Comparison 1: Cisapride versus placebo, Outcome 2: Abdominal pain
1.3
1.3. Analysis
Comparison 1: Cisapride versus placebo, Outcome 3: Abdominal distension
See this image and copyright information in PMC

Update of

Similar articles

See all similar articles

Cited by

References

References to studies included in this review

Koletzko 1990 {published data only}
    1. Koletzko S, Corey M, Ellis L, Spino M, Durie P. Effects of cisapride in patients with cystic fibrosis (CF) and chronic distal intestinal obstruction syndrome (DIOS). Pediatric Pulmonology 1989;Suppl 4:138. [CFGD REGISTER: GN15a] - PubMed
    1. Koletzko S, Corey M, Ellis L, Spino M, Stringer DA, Durie PR. Effects of cisapride in patients with cystic fibrosis and distal intestinal obstruction syndrome. Journal of Pediatrics 1990;117(5):815-22. [CFGD REGISTER: GN15b] - PubMed

References to studies excluded from this review

Baran 1980 {published data only}
    1. Baran D. Mucolytic treatment in cystic fibrosis. Double-blind clinical trial with oral acetylcysteine and placebo. European Journal of Respiratory Diseases 1980;61:134.
Dalzell 1992 {published data only}
    1. Dalzell AM, Heaf DP. High dose pancreatic enzymes in distal intestinal obstruction syndrome. Paediatric Research Society Meeting 1992;(149). [CFGD REGISTER: GN170]
Dietzsch 1980 {published data only}
    1. Dietzsch HJ, Berger G, Gottschalk B. Results of oral acetylcysteine therapy in children with cystic fibrosis. European Journal of Respiratory Diseases 1980;61:135.
Gotz 1980 {published data only}
    1. Gotz M, Kraemer R, Kerrebijn KF, Popow, C. Oral acetylcysteine in cystic fibrosis. A co-operative study. European Journal of Respiratory Diseases. Supplement 1980;111:122-6. - PubMed
Howatt 1966 {published data only}
    1. Howatt WF, DeMuth GR. A double-blind study of the use of acetylcysteine in patients with cystic fibrosis. University of Michigan Medical Center Journal 1966;32(2):82-5. - PubMed
Mitchell 1981 {published data only}
    1. Mitchell EA, Elliott RB. Failure of oral N-acetylcysteine to improve the malabsorption of cystic fibrosis. Australian Paediatric Journal 1981;17(3):207-8. - PubMed
O'Brien 2011 {published data only}
    1. O'Brien CE, Anderson PJ, Stowe CD. Lubiprostone for constipation in adults with cystic fibrosis: a pilot study. Annals of Pharmacotherapy 2011;45(9):1061-6. - PubMed
Rotolo 2019 {published data only}
    1. Rotolo N, Papale M, Parisi GF, Franzonello C, Bongiovanni A, Tardino L, et al. Treatment of distal intestinal obstruction syndrome (DIOS) in cystic fibrosis: proposal of a multicenter protocol. Italian Journal of Pediatrics 2019;45(Supplement 1):Abstract no. A22. [CFGD REGISTER: GN298]

Additional references

Alton 2017
    1. Alton EWFW, Beekman JM, Boyd AC, Brand J, Carlon MS, Connolly MM, et al. Preparation for a first-in-man lentivirus trial in patients with cystic fibrosis. Thorax 2017;72(2):137-47. - PMC - PubMed
Anderson 1990
    1. Andersen HO, Hjelt K, Waever E, Overgaard K. The age-related incidence of meconium ileus equivalent in a cystic fibrosis population:the impact of a high energy intake. Journal of Paediatric Gastroenterology and Nutrition 1990;11(3):355-60. - PubMed
BNFc 2016
    1. Joint Formulary Committee. British National Formulary for Children. Vol. 72. London: BMJ Group and Pharmaceutical Press, 2016.
Boyle 2009
    1. Boyle G, Mounsey A, Crowell K. What is the role of prokinetics for constipation. Journal of Family Practice 2009;58(4):220. - PubMed
CF Foundation 2016
    1. CF Foundation. About Cystic Fibrosis. www.cff.org/What-is-CF/About-Cystic-Fibrosis/ (accessed 13 April 2016).
Chen 2013
    1. Chen J, Ou L, Hollis S. A systematic review of the impact of routine collection of patient reported outcome measures on patients, providers and health organisations in an oncologic setting. BMC Health Service Research 2013;13:211. - PMC - PubMed
Colombo 2011
    1. Colombo C, Ellemunter H, Houwen R, Munck A, Taylor C, Wilschanski M. Guidelines for the diagnosis and management of distal intestinal obstruction syndrome in cystic fibrosis patients. Journal of Cystic Fibrosis 2011;10 Suppl 2:S24-8. [DOI: 10.1016/S1569-1993(11)60005-2] - DOI - PubMed
Davidson 1987
    1. Davidson AC, Harrison K, Steinfort CL, Geddes DM. Distal intestinal obstruction syndrome in cystic fibrosis treated by oral intestinal lavage, and a case of recurrent obstruction despite normal pancreatic function. Thorax 1987;42(7):538-41. - PMC - PubMed
Deeks 2011
    1. Deeks J, Higgins J, Altman D, editor(s) on behalf of the Cochrane Statistical Methods Group. Chapter 9 Analysing data and undertaking meta-analysis. In: Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from cochrane-handbook.org.
Dray 2004
    1. Dray X, Bienvenu T, Desmazes-Dufeu N, Dusser D, Marteau P, Hubert D. Distal intestinal obstruction syndrome in adults with cystic fibrosis. Clinical Gastroenterology and Hepatology 2004;2(6):498-503. - PubMed
Elbourne 2002
    1. Elbourne DR, Altman DG, Higgins JPT, Curtin F, Worthington HV, Vail A. Meta-analyses involving cross-over trials: methodological issues. International Journal of Epidemiology 2002;31(1):140-9. - PubMed
Ferriman 2000
    1. Ferriman A. UK licence for cisapride suspended. BMJ 2000;321(7256):259. - PMC - PubMed
Gilljam 2003
    1. Gilljam M, Chaparro C, Tullis E, Chan C, Keshavjee S, Hutcheon M. Gastrointestinal complications after lung transplantation in patients with cystic fibrosis. Chest 2003;123(1):37-41. - PubMed
Higgins 2011
    1. Higgins JPT, Altman DG, Sterne JAC, editor(s) on behalf of the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from cochrane-handbook.org.
Houwen 2010
    1. Houwen RH, Doef HP, Sermet I, Munck A, Hauser B, Walkowiak J, et al. Defining DIOS and constipation in cystic fibrosis with a multicentre study on the incidence, characteristics, and treatment of DIOS. Journal of Paediatric Gastroenterology and Nutrition 2010;50(1):38-42. [DOI: 10.1097/MPG.0b013e3181a6e01d] - DOI - PubMed
Millar‐Jones 1995
    1. Millar-Jones L, Goodchild MC. Cystic fibrosis, pancreatic sufficiency and distal intestinal obstruction syndrome: a report of four cases. Acta Paediatrica 1995;84(5):577-8. - PubMed
Moher 2009
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA Statement. PLoS Medicine 2009;6(7):e1000097. [DOI: 10.1371/journal.pmed.1000097] - DOI - PMC - PubMed
Munck 2016
    1. Munck A, Corinne A, Colombo C, Kashirskaya N, Ellemunter H, Fotoulaki M, et al on behalf of the CF/Pancreas ESPGHAN Working Group and DIOS Study Group. International prospective study of distal intestinal obstruction syndrome in cystic fibrosis: associated factors and outcome. Journal of Cystic Fibrosis 2016;15(4):531-9. - PubMed
NICE 2015
    1. National Institute for Healthcare and Excellence (NICE). Clinical knowledge summaries. Constipation in children (last revised June 2015). cks.nice.org.uk/constipation-in-children#!scenario (accessed 03 October 2016).
NICE 2017
    1. National Institute for Healthcare and Excellence (NICE). Clinical knowledge summaries. Constipation (last revised June 2017). https://cks.nice.org.uk/constipation#!prescribinginfosub:2 (accessed 25 February 2018).
Penketh 1987
    1. Penketh AR, Wise A, Mearns MB, Hodson ME, Batten JC. Cystic fibrosis in adolescents and adults. Thorax 1987;42(7):526-32. - PMC - PubMed
Ramsey 2011
    1. Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Dřevínek P, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. New England Journal of Medicine 2011;365(18):1663-72. - PMC - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Rowbotham 2017
    1. Rowbotham NJ, Smith S, Leighton PA, Rayner OC, Gathercole K, Elliott ZC, et al. The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and healthcare providers. Thorax 2017;73(4):388-90. [DOI: 10.1136/thoraxjnl-2017-210473] - DOI - PMC - PubMed
Rubinstein 1986
    1. Rubinstein S, Moss R, Lewiston N. Constipation and meconium ileus equivalent in patients with cystic fibrosis. Pediatrics 1986;78(3):473-9. - PubMed
Schunemann 2006
    1. Schunemann HJ, Fretheim A, Oxman AD. Improving the use of research evidence in guideline development: 13. Applicability, transferability and adaptation. Health Research Policy & Systems 2006;4:25. - PMC - PubMed
Sterne 2011
    1. Sterne JAC, Egger M, Moher D, editor(s) on behalf of the Cochrane Bias Methods Group. Chapter 10: Addressing reporting biases. In: Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from cochrane-handbook.org.
Tobias 2011
    1. Tobias ES, Connor M, Ferguson-Smith M. Essential Medical Genetics. 6th edition. Hoboken, NJ, USA: Wiley-Blackwell, 2011.
Tonni 1996
    1. Tonni M. Recent advances in the pharmacology of gastrointestinal prokinetics. Pharmacological Research 1996;33(4-5):217-26. - PubMed
Tuldahar 1999
    1. Tuladhar R, Daftary A, Patole SK, Whitehall JS. Oral gastrografin in neonates: a note of caution. International Journal of Clinical Practice 1999;53(7):565. - PubMed
US FDA 2016
    1. US Food and Drug Administration. Orkambi™ (lumacaftor/ivacaftor) [prescribinginformation]. www.fda.gov/Safety/MedWatch/SafetyInformation/ucm505856.htm (accessed before 18 April 2018).
Van der Doef 2010
    1. Van der Doef HPJ, Kokke FTM, Beek FJA, Woestenenk JW, Froeling SP, Houwen RHJ. Constipation in paediatric cystic fibrosis patients: an underestimated medical condition. Journal of Cystic Fibrosis 2010;9(1):59-63. - PubMed
Van der Doef 2011
    1. Van der Doef HP, Kokke FT, Ent CK, Houwen RH. Intestinal obstruction syndromes in cystic fibrosis: meconium ileus, distal intestinal obstruction syndrome, and constipation. Current Gastroenterology Reports 2011;13(3):265-70. [DOI: 10.1007/s11894-011-0185-9] - DOI - PMC - PubMed

MeSH terms