Opioid Induced Pharyngeal and Esophageal Dysfunction Clinical Trial
Official title:
Can Opioid Induced Effects on Esophageal Motility and Lower Esophageal Sphincter be Counteracted by a Dopamine Receptor Antagonist?
The purpose of this study is to determine whether a dopamine receptor antagonist metoclopramide can counteract opioid induced effects on esophageal motility and lower esophageal sphincter. The aim of this study is also to evaluate if the opioid antagonist naloxone reduces the opioid induced pharyngeal and esophageal dysfunction.
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 effect of opioid antagonists on the opioid induced pharyngeal dysfunction and lower
esophageal sphincter pressure are unknown. In a recently performed clinical trial we found
that the peripheral opioid antagonist methylnaltrexone didn't have effect on the pharyngeal
induced pharyngeal and esophageal dysfunction.This indicates that the negative opioid
induced effects are not peripherally induced or mediated via peripheral opioid receptors.
In previously performed studies most of the volunteers reported swallowing problems when
receiving infusion of the opioid remifentanil, we have also found that remifentanil
abolished spontaneous esophageal motility.
The purpose of the study is to evaluate if opioid induced effects on the lower esophageal
sphincter can be counteracted by a dopamine receptor antagonist, metoclopramide. It is
previously known that dopamine, a catecholamine neurotransmitter, decreases the lower
esophageal sphincter pressure and that a dopamine antagonist has the ability to increase the
pressure.
Further in this study we want to evaluate if the opioid antagonist naloxone, which affects
both peripheral and central opioid receptors, reduces the opioid induced pharyngeal and
esophageal dysfunction.
A third aim of the study is to evaluate if the previously reported swallowing difficulties
during infusion of opioid remifentanil are dose related, consequently does a higher
concentration of opioids increase the swallowing difficulties.
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 three years.
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Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment