Phamacological Reversal of Airway Instability During Sedation

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
Phamacological Reversal of Airway Instability During Sedation

Conditions
-----------------
Upper Airway Obstruction

Intervention / Treatment
-----------------
* Drug: Physostigmine
* Drug: Oxygen
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ages 18-45 BMI below 25 Healthy males Exclusion Criteria: Psychiatric illness Substance abuse Airway disorders Bleeding abnormatlities Claustrophobia Sleep apnea.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sedation & Physostigmine & Room Air<br>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<br>* 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.<br>* Other names: Antilirium;|
| Placebo Comparator: Sedation & Placebo & Room Air<br>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<br>* 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)<br>* Other names: Normal Saline;|
| Experimental: Sedation & Physostigmine & Oxygen<br>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<br>* 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.<br>* Other names: Antilirium;Drug: Oxygen<br>* 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.<br>|
| Placebo Comparator: Sedation & Placebo & Oxygen<br>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<br>* 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.<br>Drug: Placebo<br>* 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)<br>* Other names: Normal Saline;|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breathing, Sedation