Opioids and Esophageal Function

Is the Opioid-induced Pharyngeal and Esophageal Dysfunction Peripherally or Central Mediated?

The purpose of this study is to evaluate if opioid-induced effects on the pharynx and esophagus is centrally or peripherally mediated.

Study Overview

• Status: Completed
• Conditions: Pharyngeal Dysfunction; Esophageal Dysfunction
• Intervention / Treatment: Drug: methylnaltrexone

Detailed Description

Opioids induce pharyngeal and esophageal dysfunction and reduce the lower esophageal sphincter (LES) pressure, and thereby decreases the barrier pressure between the stomach and esophagus. This contributes to an increased risk of regurgitation and aspiration during anaesthesia induction and in the postoperative period, when the patient is treated with opioids for pain relief. The effects of opioid antagonists on the opioid induced pharyngeal dysfunction and lower esophageal sphincter pressure are unknown. Therefore it is of great clinical value to evaluate if these negative effects are reversed by peripheral opioid antagonist, methylnaltrexone.

Methylnaltrexone is one of the newer agents of peripherally acting opioid antagonists that act to reverse some of the side effects of opioid drugs, such as constipation, without affecting analgesia.

If the opioid induced pharyngeal and esophageal dysfunction and reduction of the lower esophageal sphincter pressure is peripherally induced or mediated via peripheral opioid receptors, methylnaltrexone might reverse these effects and thereby reduce postoperative morbidity by reducing pulmonary complications. On the other hand, if the dysfunction is centrally induced and not mediated via peripheral opioid receptors there is no effect of methylnaltrexone.

The pharyngeal and esophageal motility/function can be registered in an easy and objective way with the high resolution manometry, ManoScan 360. ManoScan 360 is an equipment with 36 sensors at 1 cm spacing with 12 tip transducers at every sensor. The 36 closely spaced sensors automatically capture all relevant motor function from the pharynx to the stomach. The system collects reliable and consistent data records with improved diagnostic accuracy, and the data are analyzed using ManoView analyzes software. ManoScan 360 has a CE mark approval and has been used at Örebro University Hospital during the last two years.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Örebro, Sweden, 701 85
    • Department of Anaesthesiology, University Hospital Örebro
  • Örebro, Sweden, 701 85
    • University hospital Örebro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 -40 year old healthy volunteers from both sexes.
• have signed and dated Informed Consent.
• willing and able to comply with the protocol for the duration of the trial.

Exclusion Criteria:

• anamnesis of pharyngoesophageal dysfunction.
• known or history of cardiac, pulmonary or neurological disease.
• ongoing medication.
• allergies to or history of reaction to methylnaltrexone, remifentanil or fentanyl analogues.
• pregnancy or breast feeding.
• participation in another clinical medicinal trial during the last 30 days or where follow-up is not completed.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo= normal saline	Drug: methylnaltrexone; 0,15 mg/kg sc ( subcutaneously)once per volunteer; Other Names: Relistor
Active Comparator: methylnaltexone; peripheral opioid antagonist	Drug: methylnaltrexone; 0,15 mg/kg sc ( subcutaneously)once per volunteer; Other Names: Relistor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Does methylnaltrexone influence the upper and lower esophageal sphincter pressure and the swallowing function following opioid administration?	6 hours per volunteer

Secondary Outcome Measures

Outcome Measure	Time Frame
Does methylnaltrexone influence the experience of swallowing function following opioid administration?	6 hours per volunteer

Collaborators and Investigators

• Sponsor: Region Örebro County
• Collaborators: Wyeth is now a wholly owned subsidiary of Pfizer
• Investigators: Principal Investigator: Magnus Wattwil, MD, University hospital Örebro

Publications and helpful links

General Publications

• Savilampi J, Ahlstrand R, Magnuson A, Wattwil M. Effects of remifentanil on the esophagogastric junction and swallowing. Acta Anaesthesiol Scand. 2013 Sep;57(8):1002-9. doi: 10.1111/aas.12134. Epub 2013 May 29.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: November 10, 2009
• First Submitted That Met QC Criteria: November 12, 2009
• First Posted (Estimate): November 13, 2009

Study Record Updates

• Last Update Posted (Estimate): December 9, 2011
• Last Update Submitted That Met QC Criteria: December 8, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: lower esophageal sphincter; methylnaltrexone; upper esophageal sphincter; high resolution solid state manometry; opioid induced pharyngeal and esophageal dysfunction
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Diseases; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Methylnaltrexone
• Other Study ID Numbers: JS001