Protocol for a randomised control trial of methylnaltrexone for the treatment of opioid-induced constipation and gastrointestinal stasis in intensive care patients (MOTION).

Parind B Patel,David O'Callaghan,Aisha Anjum,Anthony C Gordon,Stephen J Brett,Mary Cross,Jane Warwick

doi:10.1136/bmjopen-2016-011750

Abstract

IntroductionGastrointestinal 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.MethodsThis 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.Ethics and disseminationThe 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.Trial registration number2014-004687-37; Pre-results.

Highlights

Gastrointestinal dysmotility and constipation are common problems in intensive care patients
Other studies demonstrate that bowel dysfunction in the critically ill is associated with adverse outcomes including delay in gastric emptying leading to increased gastrooesophageal reflux and aspiration, decreased enteral feeding, delayed intensive care unit (ICU) discharge and increased mortality.[3,4,5]
While bowel dysfunction in critically ill patients is multifactorial and some component is due to the general effects of complex critical illness, exogenous and endogenous opioids contribute to this bowel dysmotility.[6]

Summary

Methods

This is a single-centre, multisite, doubleblind, randomised, placebo-controlled trial. 84 patients will be recruited from 4 intensive care units (ICUs) within Imperial College Healthcare NHS Trust. This is a single-centre, multisite, doubleblind, randomised, placebo-controlled trial. 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. Ethics and dissemination: 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). The trial results will be published in peer-reviewed journals and presented at national and international scientific meetings.

INTRODUCTION

Objectives

METHODS

Findings