Upper Airway Obstruction
Conditions
Keywords
Breathing, Sedation
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.
Interventions
DRUGPhysostigmine
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.
DRUGOxygen
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.
DRUGPlacebo
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)
Sponsors
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Ages 18-45 * BMI below 25 * Healthy males
Exclusion criteria
* Psychiatric illness * Substance abuse * Airway disorders * Bleeding abnormatlities * Claustrophobia * Sleep apnea.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AHI - Apnea Hypopnea Index | 2- 2 1/2 hours during study visit | 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 |
Countries
United States
Participant flow
Recruitment details
Dates of recruitment August 2009 to December 2010. Subjects were recruited from advertisements.
Pre-assignment details
Subjects excluded from trial before assignment to group because BMI to high, medication exclusions, lost of follow up, scheduling conflict.
Participants by arm
| Arm | Count |
|---|---|
| Physostigmine/Placebo Physostigmine (PS), a centrally-acting acetylcholinesterase inhibitor, is most commonly used by anesthesiologists in the post-anesthetic setting to reverse confusion caused by central anticholinergic medication effects. It has also been proposed as a treatment for sleep disordered breathing.We investigated whether PS was effective in decreasing the frequency of ventilatory arrhythmias (VA) produced during moderate sedation with midazolam and remifentanil in both room air (RA) and 2 l/m nasal O2. Midazolam : The sedation will be initated with a midazolam infusion with an effect-site target of 100 mg/ml intraventously Remifentanil : 0.3 mg/ml intravenously continuouslyCapsaicin : 0.075% topical cream applicationPlacebo: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. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Physostigmine/Placebo |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 24.7 years STANDARD_DEVIATION 5.7 |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
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
Time frame: 2- 2 1/2 hours during study visit
Population: This is a standard size for this type of sleep study and was performed per protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physostigmine/Oxygen | AHI - Apnea Hypopnea Index | 14.5 events per hour | Standard Deviation 21.7 |
| Placebo/Oxygen | AHI - Apnea Hypopnea Index | 27.9 events per hour | Standard Deviation 49.3 |
| Physostigmine/Room Air | AHI - Apnea Hypopnea Index | 11.3 events per hour | Standard Deviation 19.4 |
| Placebo/Room Air | AHI - Apnea Hypopnea Index | 12.1 events per hour | Standard Deviation 21.1 |