Phamacological Reversal of Airway Instability During Sedation (PHYSO)

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.

Study Overview

• Status: Completed
• Conditions: Upper Airway Obstruction
• Intervention / Treatment: Drug: Physostigmine; Drug: Placebo; Drug: Oxygen

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

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

Exclusion Criteria:

• Psychiatric illness
• Substance abuse
• Airway disorders
• Bleeding abnormatlities
• Claustrophobia
• Sleep apnea.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: 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 Names: 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.
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: 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 Names: Normal Saline; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AHI - Apnea Hypopnea Index	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	2- 2 1/2 hours during study visit

Collaborators and Investigators

• Sponsor: University of Rochester
• Investigators: Principal Investigator: Suzanne B Karan, Medical, University of Rochester

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: July 26, 2010
• First Submitted That Met QC Criteria: July 27, 2010
• First Posted (Estimate): July 28, 2010

Study Record Updates

• Last Update Posted (Estimate): April 27, 2015
• Last Update Submitted That Met QC Criteria: April 24, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Sedation; Breathing
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency; Airway Obstruction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Cholinesterase Inhibitors; Miotics; Physostigmine
• Other Study ID Numbers: 17789