Opioid-Induced Swallowing Dysfunction - The Impact of Bolus Volume

NCT ID: NCT03283020

Last Updated: 2017-12-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-11
• Study Completion Date: 2018-04-01

Brief 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.

Detailed 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.

Conditions

Pharyngeal Dysfunction; Pharyngeal Swallowing

Keywords

Remifentanil; Methylnaltrexone; Pharyngeal dysfunction; Anesthetic sedation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

RemifentanilMNTX

Volunteers are given an intravenous infusion with remifentanil, with an effect-site target concentration of 3 ng/ml via a target-controlled infusion (TCI) pump. After a series of swallowing tests an intravenous injection of methylnaltrexone of 0,3 mg/kg is given.

Group Type: ACTIVE_COMPARATOR

RemifentanilMNTX

Intervention Type: DRUG

Remifentanil infusion TCI 3 ng/ml, Methylnaltrexone injection 0.3 mg/kg

PlaceboMNTX

Volunteers are given an intravenous infusion with saline 0,9%. After a series of swallowing tests an intravenous injection of methylnaltrexone of 0,3 mg/kg is given.

Group Type: ACTIVE_COMPARATOR

PlaceboMNTX

Intervention Type: DRUG

Placebo (NaCl 0.9%) TCI infusion, Methylnaltrexone injection 0.3 mg/kg

Interventions

RemifentanilMNTX

Remifentanil infusion TCI 3 ng/ml, Methylnaltrexone injection 0.3 mg/kg

Intervention Type: DRUG

PlaceboMNTX

Placebo (NaCl 0.9%) TCI infusion, Methylnaltrexone injection 0.3 mg/kg

Intervention Type: DRUG

Other Intervention Names

Methylnaltrexone; Remifentanil; Relistor; Ultiva; Sodium Chloride 0.9%; Methylnaltrexone; Relistor

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Region Örebro County

OTHER

Sponsor Role: lead

Responsible Party

Johanna Savilampi

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Johanna Savilampi, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University hospital in Örebro

Locations

Department of Anaesthesiology and Intensive Care, Örebro University Hospital

Örebro, , Sweden

Site Status: RECRUITING

Countries

Sweden

Central Contacts

Johanna Savilampi, MD, PhD

Role: CONTACT

Phone: +46196020266

Email: johanna.savilampi@regionorebrolan.se

Facility Contacts

Johanna Savilampi, Phd

Role: primary

Per Cajander, MD

Role: backup

Other Identifiers

JS006

Identifier Type: -

Identifier Source: org_study_id