Opioid Effects on Swallowing and Esophageal Sphincter Pressure
Condition: Opioid Induced Pharyngeal and Esophageal Dysfunction
MeSH terms: Esophageal Diseases
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

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 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.
    

Intervention name(s): naloxone; remifentanil; Sodium Chloride; metoclopramide
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Injection fluid, solution 0,4 mg/kg Bolus infusion 6ug/kg at one occasion Continuous infusion 0,1 ug/kg/minute during 50 min; Powder for injection/ infusion fluid solution, 2 mg Infusion TCI 1ng/kg 10 min ( 0,05 ug/kg/min) Infusion TCI 2ng/kg 10 min ( 0.10 ug/kg/min) Infusion TCI 3ng/kg 20 min ( 0,15 ug/kg/min); Infusion fluid, solution 9 mg/ml ( hydrogenic solution ); Injection fluid, solution 5 mg/mg Iv injection 0,2 mg/kg at one occasion
Other intervention name(s): Naloxon; ACT-code: V03AB15; Ultiva; ATC-code: N01AH06; Natriumklorid; ACT-code: B05XA03; Primperan
Intervention MeSH terms: Remifentanil; Metoclopramide; Naloxone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Lower esophageal sphincter pressure; Esophageal motility; Remifentanil; Metoclopramide; Naloxone; High resolution solid state manometry