Ventilatory DepressionNCT04047550
Respiratory Control and Narcotic Effects
An observational study of Ventilatory Depression and Opioid Intoxication, run by Duke University at 1 site in United States.
Trial summary
The aim of this study is to provide data that will assess the role of ventilatory chemosensitivity (respiratory drive) in determining postoperative respiratory depression due to opioids. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ventilatory Depression, Opioid Intoxication, Opioid Toxicity
- What is being tested?
- Ventilatory chemosensitivity
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Mar 2018to 9 Feb 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients undergoing surgery requiring opioids for postoperative analgesia
Who may be able to join
- 18 years of age or older, undergoing major abdominal or urological surgery requiring at least one overnight hospital stay
Who cannot join
- Pregnancy Adverse reaction to remifentanil Opioid-use within the past month Dependency on supplemental oxygen Brain injury in the past year Coronary artery disease Sickle cell disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: Respiratory Control and Prevention of Opioid-Induced Respiratory Depression After Surgery
The aim of this study is to provide data that will assess the role of ventilatory chemosensitivity (respiratory drive) in determining postoperative respiratory depression due to opioids. In a group of patients requiring surgery and admission to hospital, before surgery, ventilatory chemosensitivity will be assessed in the presence or absence of an infusion of remifentanil. Parameters will be correlated with ventilatory depression events after surgery. A secondary aim is to determine whether respiratory depression is more likely during specific phases of sleep.
Read the detailed description
The study aims to test the following hypotheses:
Low respiratory drive is predictive of opioid-induced respiratory depression as defined by end-tidal PCO2 (PETCO2) >50 mmHg, ventilation <20% below baseline or pulse oximeter reading (SpO2) <90%.
Respiratory depression is more likely during certain sleep stages, specifically slow wave sleep.
Respiratory Drive. Before surgery each patient's hypercapnic ventilatory response under conditions of mild hypoxia and mild hyperoxia. Using this technique, the patient first voluntarily hyperventilates to a PETCO2 value of 20-25 mmHg, then undergoes a rebreathing test allowing the PCO2 to rise to 55-60 mmHg while end-tidal PO2 (PETO2) is maintained at 150 mmHg. The procedure is then repeated with PETO2 clamped at 50 mmHg. Parameters derived from this method include slopes of the ventilatory response during hyperoxia and hypoxia. The slope during mild hypoxia is felt to be an index of peripheral chemoreceptor function, while the hyperoxic slope is more indicative of central respiratory drive.
These two maneuvers will then be repeated during an infusion of the ultra-short acting opioid, remifentanil. Remifentanil will be administered to achieve a specified effect site concentration selected to produce a 30% decrease in ventilation using a standard pharmacokinetic model implemented on a widely-used shareware program (TIVATrainer, www.eurosaver.eu). Recovery from ventilatory depression occurs within 10 minutes of discontinuation of the infusion.
Sleep Test. During a night before surgery a sleep test based on peripheral arterial tone will be performed at home (WatchPAT™, Itamar Medical, Franklin, MA) and will provide a formal measure of obstructive sleep apnea. This test requires only a device mounted on a finger that assesses SpO2 and peripheral tone, and an accelerometer on the chest to assess breathing movements. Respiratory indices calculated using this technology correlates with those calculated from standard polysomnography. The same testing will be used postoperatively from the time the patient enters the post anesthesia care unit (PACU) until the following morning. Recording of the same variables will then continue: inter-breath interval, respiratory minute volume (using an electrical impedance device: ExSpiron™, Respiratory Motion, Waltham, MA), abdominal strain gauge recording, transcutaneous PCO2 (SenTec, Fenton, MO), and sleep measures. The data stream will then be divided into 5 minute epochs. During each epoch the sleep state (awake, stages 1-4 slow wave sleep, rapid eye movement (REM) sleep), opioid consumption, respiratory variables and apnea/hypopnea index (AHI) will be assessed. Subjects will have the option to opt in or out of participation in the overnight sleep study.
Long-Term Pulse Oximetry. For the entire postoperative period until discharge we will record opioid consumption and SpO2/heart rate using a wrist oximeter (WristOx™, Nonin Medical, Plymouth, MN).
Postoperative parameters of respiratory depression include hypercapnia (transcutaneous PCO2), hypoxemia, apneas, low respiratory minute volume and sleep state.
- Conditions
- Ventilatory Depression, Opioid Intoxication, Opioid Toxicity
- Being tested
- Ventilatory chemosensitivity
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ventilatory chemosensitivityDiagnostic test
Using this technique, the patient first voluntarily hyperventilates to a PETCO2 value of 20-25 mmHg, then undergoes a rebreathing test allowing the PCO2 to rise to 55-60 mmHg while PETO2 is maintained at 150 mmHg. The procedure is then repeated with PETO2 clamped at 50 mmHg. Parameters derived from this method include slopes of the ventilatory response during hyperoxia and hypoxia.
What is being measured
The primary outcome is the main question the study is designed to answer.
Opioid related respiratory depression (OIRD) frequency
A respiratory event is defined as one or more of the following:
- Respiratory rate <60% of baseline
- Minute ventilation (MV) <60% of predicted value based on body surface area (BSA). Predicted MV for men=4 x BSA, for women=3.5 x BSA
- Pulse oximeter reading (SpO2) <90% (breathing room air) or <92% (breathing supplemental O2)
- Transcutaneous PCO2 >50 mmHg
- Central or obstructive apnea/hypopnea detected by WatchPAT (Itamar Medical, Atlanta, GA) based on decrease in peripheral arterial tone amplitude, increase in heart rate and decrease in SpO2 ≥3% or snoring in the absence of body movement.
Events must last 1 minute or more to be counted. Events occurring within one minute of each are combined as a single event.
Measured: From the arrival of the patient in the post anesthesia care unit until the first postoperative morning
Secondary outcomes (1)
Frequency of OIRD during specific sleep stages
OIRD as defined in the primary outcome, as a function of sleep stage postoperatively, as measured using the WatchPAT™ (Itamar Medical, Franklin, MA)
Measured: From the arrival of the patient in the post anesthesia care unit until the first postoperative morning
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2019
- Study start8 Mar 2018
- Primary completion9 Feb 2019
- Study completion9 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ventilatory DepressionStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Richard E Moon, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04047550
- Sponsor's protocol ID
- Pro00046973
- Status last verified
- Aug 2020
- First submitted
- 5 Aug 2019
- Last updated
- 27 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Respiratory Control and Prevention of Opioid-Induced Respiratory Depression After Surgery
- ClinicalTrials.gov ID
- NCT04047550
- Acronym / sponsor ID
- Pro00046973
- Conditions
- Ventilatory Depression, Opioid Intoxication, Opioid Toxicity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- 8 Mar 2018 (actual)
- Primary completion
- 9 Feb 2019 (actual)
- Study completion
- 9 Feb 2019 (actual)
- First posted
- 6 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to provide data that will assess the role of ventilatory chemosensitivity (respiratory drive) in determining postoperative respiratory depression due to opioids. In a group of patients requiring surgery and admission to hospital, before surgery, ventilatory chemosensitivity will be assessed in the presence or absence of an infusion of remifentanil. Parameters will be correlated with ventilatory depression events after surgery. A secondary aim is to determine whether respiratory depression is more likely during specific phases of sleep.
Detailed description
The study aims to test the following hypotheses:
Low respiratory drive is predictive of opioid-induced respiratory depression as defined by end-tidal PCO2 (PETCO2) >50 mmHg, ventilation <20% below baseline or pulse oximeter reading (SpO2) <90%.
Respiratory depression is more likely during certain sleep stages, specifically slow wave sleep.
Respiratory Drive. Before surgery each patient's hypercapnic ventilatory response under conditions of mild hypoxia and mild hyperoxia. Using this technique, the patient first voluntarily hyperventilates to a PETCO2 value of 20-25 mmHg, then undergoes a rebreathing test allowing the PCO2 to rise to 55-60 mmHg while end-tidal PO2 (PETO2) is maintained at 150 mmHg. The procedure is then repeated with PETO2 clamped at 50 mmHg. Parameters derived from this method include slopes of the ventilatory response during hyperoxia and hypoxia. The slope during mild hypoxia is felt to be an index of peripheral chemoreceptor function, while the hyperoxic slope is more indicative of central respiratory drive.
These two maneuvers will then be repeated during an infusion of the ultra-short acting opioid, remifentanil. Remifentanil will be administered to achieve a specified effect site concentration selected to produce a 30% decrease in ventilation using a standard pharmacokinetic model implemented on a widely-used shareware program (TIVATrainer, www.eurosaver.eu). Recovery from ventilatory depression occurs within 10 minutes of discontinuation of the infusion.
Sleep Test. During a night before surgery a sleep test based on peripheral arterial tone will be performed at home (WatchPAT™, Itamar Medical, Franklin, MA) and will provide a formal measure of obstructive sleep apnea. This test requires only a device mounted on a finger that assesses SpO2 and peripheral tone, and an accelerometer on the chest to assess breathing movements. Respiratory indices calculated using this technology correlates with those calculated from standard polysomnography. The same testing will be used postoperatively from the time the patient enters the post anesthesia care unit (PACU) until the following morning. Recording of the same variables will then continue: inter-breath interval, respiratory minute volume (using an electrical impedance device: ExSpiron™, Respiratory Motion, Waltham, MA), abdominal strain gauge recording, transcutaneous PCO2 (SenTec, Fenton, MO), and sleep measures. The data stream will then be divided into 5 minute epochs. During each epoch the sleep state (awake, stages 1-4 slow wave sleep, rapid eye movement (REM) sleep), opioid consumption, respiratory variables and apnea/hypopnea index (AHI) will be assessed. Subjects will have the option to opt in or out of participation in the overnight sleep study.
Long-Term Pulse Oximetry. For the entire postoperative period until discharge we will record opioid consumption and SpO2/heart rate using a wrist oximeter (WristOx™, Nonin Medical, Plymouth, MN).
Postoperative parameters of respiratory depression include hypercapnia (transcutaneous PCO2), hypoxemia, apneas, low respiratory minute volume and sleep state.
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients undergoing surgery requiring opioids for postoperative analgesia
Key inclusion criteria (1 listed)
- 18 years of age or older, undergoing major abdominal or urological surgery requiring at least one overnight hospital stay
Key exclusion criteria (1 listed)
- Pregnancy Adverse reaction to remifentanil Opioid-use within the past month Dependency on supplemental oxygen Brain injury in the past year Coronary artery disease Sickle cell disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ventilatory chemosensitivityUsing this technique, the patient first voluntarily hyperventilates to a PETCO2 value of 20-25 mmHg, then undergoes a rebreathing test allowing the PCO2 to rise to 55-60 mmHg while PETO2 is maintained at 150 mmHg. The procedure is then repeated with PETO2 clamped at 50 mmHg. Parameters derived from this method include slopes of the ventilatory response during hyperoxia and hypoxia. | Diagnostic test | – |
Primary outcome
Opioid related respiratory depression (OIRD) frequency
Time frame: From the arrival of the patient in the post anesthesia care unit until the first postoperative morning
A respiratory event is defined as one or more of the following: 1. Respiratory rate <60% of baseline 2. Minute ventilation (MV) <60% of predicted value based on body surface area (BSA). Predicted MV for men=4 x BSA, for women=3.5 x BSA 3. Pulse oximeter reading (SpO2) <90% (breathing room air) or <92% (breathing supplemental O2) 4. Transcutaneous PCO2 >50 mmHg 5. Central or obstructive apnea/hypopnea detected by WatchPAT (Itamar Medical, Atlanta, GA) based on decrease in peripheral arterial tone amplitude, increase in heart rate and decrease in SpO2 ≥3% or snoring in the absence of body movement. Events must last 1 minute or more to be counted. Events occurring within one minute of each are combined as a single event.
1 secondary outcome
Frequency of OIRD during specific sleep stages
Time frame: From the arrival of the patient in the post anesthesia care unit until the first postoperative morning
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2020.
- Individual participant dataSharing planned: No
Related trials for Ventilatory Depression
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Phase Resolved Functional Lung MRI and Oscillometry for the Observation of Healthy Lung Function
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Clinical Evaluation of an Alarm Activated Detection System to Enable Early Intervention of Emerging Respiratory Decline With the Linshom Medical Continuous Predictive Respiratory Sensor (CPRS)
Post Surgical Respiratory Failure, Respiratory Complication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard E Moon, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ventilatory Depression and Opioid Intoxication, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Opioid related respiratory depression (OIRD) frequency (time frame: From the arrival of the patient in the post anesthesia care unit until the first postoperative morning). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2020.