title: Protocol for a randomised control trial of methylnaltrexone for the treatment of opioid-induced constipation and gastrointestinal stasis in intensive care patients (MOTION).
abstract: Gastrointestinal dysmotility and constipation are common problems in intensive care patients. The majority of critical care patients are sedated with opioids to facilitate tolerance of endotracheal tubes and mechanical ventilation, which inhibit gastrointestinal motility and lead to adverse outcomes. Methylnaltrexone is a peripheral opioid antagonist that does not cross the blood-brain barrier and can reverse the peripheral side effects of opioids without affecting the desired central properties. This trial will investigate whether methylnaltrexone can reverse opioid-induced constipation and gastrointestinal dysmotility.
  
  
  
  This is a single-centre, multisite, double-blind, randomised, placebo-controlled trial. 84 patients will be recruited from 4 intensive care units (ICUs) within Imperial College Healthcare NHS Trust. Patients will receive intravenous methylnaltrexone or placebo on a daily basis if they are receiving opioid infusion to facilitate mechanical ventilation and have not opened their bowels for 48 hours. All patients will receive standard laxatives as per the clinical ICU bowel protocol prior to randomisation. The primary outcome of the trial will be time to significant rescue-free laxation following randomisation. Secondary outcomes will include tolerance of enteral feed, gastric residual volumes, incidence of pneumonia, blood stream and Clostridium difficile infection, and any reversal of central opioid effects.
  
  
  
  The trial protocol, the patient/legal representative information sheets and consent forms have been reviewed and approved by the Harrow Research Ethics Committee (REC Reference 14/LO/2004). An independent Trial Steering Committee and Data Monitoring Committee are in place, with patient representation. On completion, the trial results will be published in peer-reviewed journals and presented at national and international scientific meetings.
  
  
  
  2014-004687-37; Pre-results.
authors.affiliation: Centre for Perioperative Medicine and Critical Care Research, Imperial College Healthcare NHS Trust, London, UK Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Parind B
authors.initials: PB
authors.lastname: Patel
authors.affiliation: Centre for Perioperative Medicine and Critical Care Research, Imperial College Healthcare NHS Trust, London, UK Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Brett
authors.affiliation: Centre for Perioperative Medicine and Critical Care Research, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: O'Callaghan
authors.affiliation: Imperial Clinical Trials Unit, Faculty of Medicine, School of Public Health, Imperial College London, London, UK.
authors.forename: Aisha
authors.initials: A
authors.lastname: Anjum
authors.affiliation: Imperial Clinical Trials Unit, Faculty of Medicine, School of Public Health, Imperial College London, London, UK.
authors.forename: Mary
authors.initials: M
authors.lastname: Cross
authors.affiliation: Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Warwick
authors.affiliation: Centre for Perioperative Medicine and Critical Care Research, Imperial College Healthcare NHS Trust, London, UK Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Gordon
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects*; D001812:Blood-Brain Barrier; D003248:Constipation / Q000188:drug therapy* / Q000209:etiology; D003422:Critical Care; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D054368:Laxatives / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000701:Analgesics, Opioid; D054368:Laxatives; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone