Phamacological Reversal of Airway Instability During Sedation (PHYSO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Suzanne Karan, University of Rochester
ClinicalTrials.gov Identifier:
NCT01171118
First received: July 26, 2010
Last updated: July 2, 2012
Last verified: July 2012
  Purpose

The investigators are attempting to demonstrate a decrease in the frequency and severity of sedation-induced respiratory arrhythmias(central and obstructive apneas) with pharmacological pre-treatment in this pilot project and then eventually to understand the mechanisms behind this decrease. The efficacy and mechanisms of these treatments, while evaluated during sleep in Obstructed Sleep Apnea (OSA) patients, have not been systematically studied during sedation in either normal subjects or OSA patients. The agent to be assessed in this study in physostigmine versus placebo.


Condition Intervention
Upper Airway Obstruction
Drug: Midazolam
Drug: Remifentanil
Drug: Capsaicin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Phamacological Reversal of Airway Instability During Sedation

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • EEG activity [ Time Frame: 2- 2 1/2 hours during study visit ] [ Designated as safety issue: Yes ]
    These measures will be used to directly assess CNS arousability during the changes in airway pressure via power spectral analytic measure of Alpha, Beta and Gamma frequency EEG


Secondary Outcome Measures:
  • BIS monitor [ Time Frame: 2-2 1/2 hours during the study visit ] [ Designated as safety issue: Yes ]
    This is a clinically useful monitor of sedation and will allow the sedation state achieved in the laboratory setting to be related to clinical sedation. It will also provide a quantitative correlation of the OAA/S and the pain VAS scores.


Enrollment: 18
Study Start Date: August 2009
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Physostigmine
The Increased cholinergic activeity caused by this drug includes increased secretions and peristaltic activity, and bradycardia. Both are generally minimal but an anti-cholinergic agent (glycopyrrolate) will be available at the bedside.We are attempting to demonstrate a decrease in the frequency and severity of sedation-induced respiratory arrhythmias (central and obstructive apneas) with pharmacological pre-treatment in this pilot project and then eventually to understand the mechanisms behind this decrease. The efficacy and mechanisms of these treatments, while evaluated during sleep in OSA patients, have not been systematically studied during sedation in either normal subjects or OSA patients. The agent to be assessed in this study is physostigmine versus placebo.
Drug: Midazolam
The sedation will be initated with a midazolam infusion with an effect-site target of 100 mg/ml intraventously
Other Name: Versed
Drug: Remifentanil
0.3 mg/ml intravenously continuously
Other Name: Ultiva
Drug: Capsaicin
0.075% topical cream applied
Placebo Comparator: Placebo
We are attempting to demonstrate a decrease in the frequency and severity of sedation-induced respiratory arrhythmias (central and obstructive apneas) with pharmacological pre-treatment in this pilot project and then eventually to understand the mechanisms behind this decrease. The efficacy and mechanisms of these treatments, while evaluated during sleep in OSA patients, have not been systematically studied during sedation in either normal subjects or OSA patients. The agent to be assessed in this study is physostigmine versus placebo.
Drug: Midazolam
The sedation will be initated with a midazolam infusion with an effect-site target of 100 mg/ml intraventously
Other Name: Versed
Drug: Remifentanil
0.3 mg/ml intravenously continuously
Other Name: Ultiva
Drug: Capsaicin
0.075% topical cream applied

Detailed Description:

One of the most serious side effects of drugs administered for sedation is untoward respiratory events. The relative prevalence of such events is thought to be high, occurring in up to 41% of patients in some cohorts. Many specific drugs and combinations have been recommended for moderate sedation, particularly when provided by a non-anesthesiologist. The use of an opioid and a benzodiazepine is the most frequent combination, partly because the availability of antagonists for both drugs may make a "rescue" easier. However, this combination results in frequent respiratory arrhythmias (combinations of obstructions, pauses and changes in respiratory patterns).There has not been a comprehensive study of the mechanisms underlying the disruptions of respiratory rhythm caused by agents commonly used for moderate sedation. This specific research, and the line of research it opens, has the potential to make the administration of anxiolytics and analgesics safer for patients at high risk for respiratory events.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Ages 18-45
  • BMI below 25
  • Healthy males

Exclusion Criteria:

  • Psychiatric illness
  • Substance abuse
  • Airway disorders
  • Bleeding abnormatlities
  • Claustrophobia
  • Sleep apnea.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01171118

Locations
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
Sponsors and Collaborators
University of Rochester
Investigators
Principal Investigator: Suzanne B Karan, Medical University of Rochester
  More Information

No publications provided

Responsible Party: Suzanne Karan, Principal investigator, University of Rochester
ClinicalTrials.gov Identifier: NCT01171118     History of Changes
Other Study ID Numbers: 17789
Study First Received: July 26, 2010
Last Updated: July 2, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Rochester:
Breathing
Sedation

Additional relevant MeSH terms:
Airway Obstruction
Respiratory Insufficiency
Respiration Disorders
Respiratory Tract Diseases
Capsaicin
Remifentanil
Physostigmine
Midazolam
Antipruritics
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adjuvants, Anesthesia
Central Nervous System Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Cholinesterase Inhibitors

ClinicalTrials.gov processed this record on August 18, 2014