Opioid-Induced Swallowing Dysfunction - The Impact of Bolus Volume

Pharyngeal Dysfunction Clinical Trial

Official title:

Opioid-Induced Swallowing Dysfunction - The Impact of Bolus Volume: a Randomized, Double-Blind Study in Healthy Volunteers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03283020
• Other study ID #: JS006
• Status: Recruiting
• Phase: Phase 4
• First received: September 12, 2017
• Last updated: December 11, 2017
• Start date: November 11, 2017
• Est. completion date: April 1, 2018

Study information

• Verified date: December 2017
• Source: Region Örebro County
• Contact: Johanna Savilampi, MD, PhD
• Phone: +46196020266
• Email: johanna.savilampi[@]regionorebrolan.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the impact of different bolus volumes and viscosity on remifentanil-induced swallowing dysfunction in healthy volunteers.Hence, whether swallowing tasks can be done safer during sedation by altering bolus volumes and viscosities will be revealed. Furthermore, the study will clarify underlying mechanisms (central vs. peripheral effects) of remifentanil-induced swallowing dysfunction. If methylnaltrexone reverses the remifentanil-induced effects on swallowing, this would suggest a dominant peripherally mediated mechanism.

Description:

Monitored anesthesia care (MAC) is commonly applied in modern perioperative care and means that minor surgical procedures are accomplished in awake patients using local anesthesia and light sedation. MAC has many advantages compared to general anesthesia; the recovery time after anesthesia is shorter and risk for postoperative nausea is lower to mention some. However, the patient is spontaneously breathing and the airway is not protected by an endotracheal tube which potentially increases risk of pulmonary aspiration. Pulmonary aspiration, that is inhalation of stomach and/or pharyngeal contents into the lungs, is a severe anesthesia-related complication and can in worst case lead to pneumonia and even death. Intact swallowing function is crucial in avoiding aspiration and how sedatives and analgesic agents used during MAC influence swallowing function is not fully understood.

Pharyngeal function during bolus swallowing is measured by combined high resolution impedance manometry (HRIM). The HRIM catheter is inserted through the nose in such a way that sensors straddle the entire pharynx and esophagus with the distal catheter tip in the stomach. Dynamic pressure changes and flow can be detected during swallowing and data registered by HRIM are analysed using purpose-designed software, AIM analysis (automated impedance manometry analysis). AIM analysis derives pressure flow variables which describe different physiological events like bolus timing and bolus distension in the pharynx and the esophagus during swallowing. A Swallow Risk Index value, quantifying risk of deglutitive aspiration, can also be defined.

The aim of the study is to evaluate impact of different bolus volumes on remifentanil-induced swallowing dysfunction in healthy volunteers. The study will clarify underlying mechanisms (central vs. peripheral effects) of remifentanil-induced swallowing dysfunction. Furthermore, whether swallowing tasks can be done safer during sedation by altering bolus volumes will be revealed. In addition to bolus volume, different bolus viscosities will be tested. It is shown that higher bolus viscosity diminishes misdirected swallows in dysphagic patients and higher bolus viscosity may possibly counteracts the swallowing dysfunction induced by remifentanil. Moreover, if MNTX reverses the remifentanil-induced effects on swallowing, then this would suggest a dominant peripherally mediated mechanism. Our aim is also to evaluate impact of remifentanil exposure on esophageal motility and impact of methylnaltrexone alone on swallowing function.

20 healthy volunteers will be studied on two different occasions approximately one week apart. In a randomized order volunteers will receive intravenous infusion of remifentanil and an intravenous injection of MNTX on one occasion, and placebo (normal saline) infusion and an intravenous injection of MNTX on the other occasion. Blood samples are obtained for plasma concentration determination of the study drug and sedation levels are assessed during study drug exposure.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: April 1, 2018
• Est. primary completion date: April 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

1. = 18 - = 40 year old healthy volunteers from both sexes.

2. Have signed and dated Informed Consent.

3. Willing and able to comply with the protocol for the duration of the trial.

Exclusion Criteria:

1. Anamnesis of pharyngoesophageal dysfunction.

2. Known or history of gastrointestinal, severe cardiac, pulmonary or neurological disease

3. Ongoing medication that may affect upper gastrointestinal tract, larynx or lower airway.

4. Allergies to or history of reaction to remifentanil, fentanyl analogues or dexmedetomidine.

5. Pregnancy or breast feeding

6. BMI > 30

7. Smoking

8. Previous participation in a medicinal clinical trial during the last year where an opioid has been used or have during the last 30 days participated in any other medicinal clinical trial or in a trial where follow-up is not completed.

Related Conditions & MeSH terms

• Pharyngeal Dysfunction
• Pharyngeal Swallowing

Intervention

Drug:
• RemifentanilMNTX
Remifentanil infusion TCI 3 ng/ml, Methylnaltrexone injection 0.3 mg/kg
• PlaceboMNTX
Placebo (NaCl 0.9%) TCI infusion, Methylnaltrexone injection 0.3 mg/kg

Locations

Country	Name	City	State
Sweden	Department of Anaesthesiology and Intensive Care, Örebro University Hospital	Örebro

Sponsors (1)

Lead Sponsor	Collaborator
Region Örebro County

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pressure Flow pharyngeal variables, 10 ml vs 20 ml bolus	Difference in pharyngeal pressure flow variables during remifentanil exposure between bolus volumes of 10 ml and 20 ml compared to placebo.	Up to 60 minutes
Secondary	Pressure Flow pharyngeal variables, liquid vs semisolid bolus	Difference in pharyngeal pressure flow variables during remifentanil exposure between liquid and semisolid boluses compared to placebo	Up to 60 minutes
Secondary	Pressure Flow pharyngeal variables, remifentanil before vs after methylnaltrexone	Difference in pharyngeal pressure flow variables during remifentanil exposure before and after methylnaltrexone administration compared to placebo.	Up to 60 minutes
Secondary	Pressure Flow pharyngeal variables, placebo before vs after methylnaltrexone	Difference in pharyngeal pressure flow variables during placebo infusion before and after methylnaltrexone administration.	Up to 60 minutes
Secondary	Pressure Flow esophageal motility variables, 10 ml vs 20 ml bolus	Difference in variables of esophageal motility between different bolus volumes during remifentanil exposure compared to placebo.	Up to 60 minutes
Secondary	Pressure Flow esophageal motility variables, liquid vs semisolid bolus	Difference in variables of esophageal motility between liquid and semisolid boluses during remifentanil exposure compared to placebo.	Up to 60 minutes
Secondary	Pressure Flow esophageal motility variables, remifentanil before vs after methylnaltrexone	Difference in variables of esophageal motility during remifentanil exposure before and after methylnaltrexone administration compared to placebo.	Up to 60 minutes
Secondary	Pressure Flow esophageal motility variables, placebo before vs after methylnaltrexone	Difference in variables of esophageal motility during placebo infusion before and after methylnaltrexone administration.	Up to 60 minutes