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: April 24, 2015
Last verified: April 2015
  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: Physostigmine
Drug: Oxygen
Drug: Placebo

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:
  • AHI - Apnea Hypopnea Index [ Time Frame: 2- 2 1/2 hours during study visit ] [ Designated as safety issue: Yes ]
    This is a standard metric used to describe severity of disordered breathing during sleep.Normal healthy subjects would have an AHI value of zero during sleep. Mild disordered breathing would correspond to a value of 5 to 10 events per hours; moderate 10-25; severe would be over 25


Enrollment: 10
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: Sedation & Physostigmine & Room Air
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.We are interested in the effect of breathing oxygen vs. room air on the regulation of respiratory control during moderate sedation.
Drug: Physostigmine
Physostigmine is a centrally acting acetylcholinesterase inhibitor that has been proposed as a treatment for sleep disordered breathing. It is currently FDA approved and used commonly by Anesthesiologists in the post anesthetic setting to reverse confusion caused by central anticholinergic medication effects.
Other Name: Antilirium
Placebo Comparator: Sedation & Placebo & Room Air
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.We are interested in the effect of breathing oxygen vs. room air on the regulation of respiratory control during moderate sedation.
Drug: Placebo
The administration of placebo versus physostigmine was untertaken in the same sedation conditions on the alternate day in each subject (and with both room air and oxygen)
Other Name: Normal Saline
Experimental: Sedation & Physostigmine & Oxygen
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.We are interested in the effect of breathing oxygen vs. room air on the regulation of respiratory control during moderate sedation.
Drug: Physostigmine
Physostigmine is a centrally acting acetylcholinesterase inhibitor that has been proposed as a treatment for sleep disordered breathing. It is currently FDA approved and used commonly by Anesthesiologists in the post anesthetic setting to reverse confusion caused by central anticholinergic medication effects.
Other Name: Antilirium
Drug: Oxygen
The administration of nasal cannula-administered oxygen at a flow rate of 2 liters/minute is commonly performed during clinical sedation practice. Thus, this experiment employed its use to compare respiratory effects of oxygen versus room air.
Other Name: Oxygen
Placebo Comparator: Sedation & Placebo & Oxygen
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.We are interested in the effect of breathing oxygen vs. room air on the regulation of respiratory control during moderate sedation.
Drug: Oxygen
The administration of nasal cannula-administered oxygen at a flow rate of 2 liters/minute is commonly performed during clinical sedation practice. Thus, this experiment employed its use to compare respiratory effects of oxygen versus room air.
Other Name: Oxygen
Drug: Placebo
The administration of placebo versus physostigmine was untertaken in the same sedation conditions on the alternate day in each subject (and with both room air and oxygen)
Other Name: Normal Saline

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
Results First Received: March 8, 2013
Last Updated: April 24, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Rochester:
Breathing
Sedation

Additional relevant MeSH terms:
Airway Obstruction
Respiration Disorders
Respiratory Insufficiency
Respiratory Tract Diseases
Physostigmine
Autonomic Agents
Cholinergic Agents
Cholinesterase Inhibitors
Enzyme Inhibitors
Miotics
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2015