HealthyTCINCT01759160
Hemodynamic Responses During Induction: Comparison of Marsh and Schnider Pharmacokinetic Models
A study testing Marsh Plasma TCI with high initial target and Schnider Plasma TCI with high initial target in people with Healthy, run by First Affiliated Hospital, Sun Yat-Sen University at 1 site in China.
Trial summary
To compare the hemodynamic changes during anesthesia induction between Marsh and Schnider plasma TCI models. We put forward a hypothesis that, if one TCI model is associated with much more prominent vasodilation effect or cardiac depression, a more sharp decrease in mean arterial pressure, systemic vascular resistance… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Marsh Plasma TCI with high initial target and Schnider Plasma TCI with high initial target
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- Dec 2012to Jan 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Patients between the ages of 18 years and 70 years
- ASA physical status I and II
- surgical procedures requiring general anesthesia with continuous CVP and arterial pressure monitoring.
Who cannot join
- Patients younger than 16 y or older than 65 y
- Body Mass Index (BMI) <18 or >30
- emergency surgery
- allergy to any of the drugs used
- inability to communicate effectively
- severe cardiovascular dysfunction
- patient refusal and patients on long-term opioids or sedative medication.
Trial locations and contacts
1 site in 1 country.
China1 site
The First Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510080
About this study
Official title: Hemodynamic Responses During Induction: Comparison of Marsh and Schnider Pharmacokinetic Models in Propofol Plasma Target-controlled Infusion
To compare the hemodynamic changes during anesthesia induction between Marsh and Schnider plasma TCI models. We put forward a hypothesis that, if one TCI model is associated with much more prominent vasodilation effect or cardiac depression, a more sharp decrease in mean arterial pressure, systemic vascular resistance , central venous return or stroke volume would be observed.
Read the detailed description
Current systems of propofol TCI are pre-programmed with the Marsh and Schnider pharmacokinetic models. Rate constants of Marsh are fixed, whereas compartment volumes and clearances are weight proportional. Schnider model has fixed values for VC, V3, k13, and k31, adjusts V2, k12, and k21 for age, and adjusts k10 according to total weight, lean body mass (LBM), and height. One major benefit of the Schnider model is that it adjusts doses and infusion rates according to patient age. This provides a strong argument for using the Schnider model in the elderly and unwell patients which may improve hemodynamic stability and safety.
However for the vast majority of young and middle age patients, whether Marsh or Schnider would be a better choice for hemodynamic stability remains unknown.
With marsh model, as VC is scaled to body weight, the amount of drug delivered is dependent of body weight. In the Schnider model, as VC at 4.27L is independent of body weight, VC in terms of ml/kg decreases as body weight increases. This and the influence of height and weight on clearance results in heavier patients receiving less propofol on a mg/kg basis whereas those with a lower lean body mass will initially receive about 30% less than delivered by Marsh, but after 30 min, the Schnider model delivers about 15% more. Besides, when Schnider model is used in the morbidly obese, the LBM equation can generate paradoxical values resulting in excessive increases in maintenance infusion rates. Nevertheless, the purpose of this study was to investigate the vast majority of Asian patients whose body weight were in normal range. Only patients with BMI between 18 and 29 were included to minimize the influential factor of body weight in TCI system.
To compare the hemodynamic changes during anesthesia induction between Marsh and Schnider plasma TCI models. We put forward a hypothesis that, if one TCI model is associated with much more prominent vasodilation effect or cardiac depression, a more sharp decrease in mean arterial pressure, systemic vascular resistance , central venous return or stroke volume would be observed.
- Conditions
- Healthy
- Being tested
- Marsh Plasma TCI with high initial target, Schnider Plasma TCI with high initial target
- Keywords
- Target control infusion, propofol, cardiac depression, induction of anesthesia, hemodynamics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Marsh Plasma TCI with high initial targetProcedure or surgery
Also called Plasma target-controlled infusion in Marsh model
plasma target-controlled infusion in Marsh model(n=30) with an initial target concentration of 4 μg/ml. Target was then reset and gradually titrated to a sedation level with narcotrend index below 64.
Schnider Plasma TCI with high initial targetProcedure or surgery
Also called Plasma target-controlled infusion in Schnider model
plasma target-controlled infusion in Schnider model(n=30) with an initial target concentration of 4 μg/ml. Target was then reset and gradually titrated to a sedation level with narcotrend index below 64.
| Study group | Role | What they receive |
|---|---|---|
| Marsh | Active comparator | Marsh Plasma TCI with high initial target Receives: Procedure: Marsh Plasma TCI with high initial target |
| Schnider | Active comparator | Schnider Plasma TCI with high initial target Receives: Procedure: Schnider Plasma TCI with high initial target |
What is being measured
The primary outcome is the main question the study is designed to answer.
SVI (Stroke Volume Index) Value Change From Baseline Level at the End of the First 25 Minutes.
After propofol infusion started, according to sedation level, TCI targets were gradually titrated to reach a state of equilibrium at the end of the first 25 minutes. SVI were continuously monitored, at the end of the first 25 minutes, value change from baseline level were calculated.
Measured: The end of the first 25 minutes after propofol infusion
Secondary outcomes (2)
NI (Narcotrend Index) Reduction
Narcotrend was utilized to continuously record patients' sedation level during induction, provided as a criteria for Cpt (Plasma Target Concentration) adjustment.
Measured: 25 minutes after propofol infusion
CVP (Central Venous Pressure)
CVP was continuously monitored to assess preload condition and served to calculate SVRI (systemic vascular resistance index) every minute during the first 25 minutes of infusion.
Measured: 25 minutes after induction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2013 (estimated)
- Study startDec 2012
- Primary completionJan 2013
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by First Affiliated Hospital, Sun Yat-Sen 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xia Feng, First Affiliated Hospital, Sun Yat-Sen University
- Investigators
- Xia Feng, M.D., Principal investigator, The First Affiliaed Hospital of Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01759160
- Sponsor's protocol ID
- NSFCfengxiar1
- Other IDs
- Fengxia1
- Acronym
- TCI
- Status last verified
- Mar 2013
- First submitted
- 20 Dec 2012
- Last updated
- 29 Mar 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Yang XY, Zhou ZB, Yang L, Zhou X, Niu LJ, Feng X. Hemodynamic responses during induction: comparison of Marsh and Schnider pharmacokinetic models. Int J Clin Pharmacol Ther. 2015 Jan;53(1):32-40. doi: 10.5414/CP202141.
PubMed 25500489
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hemodynamic Responses During Induction: Comparison of Marsh and Schnider Pharmacokinetic Models in Propofol Plasma Target-controlled Infusion
- ClinicalTrials.gov ID
- NCT01759160
- Acronym / sponsor ID
- TCI / NSFCfengxiar1
- Conditions
- Healthy
- Keywords
- Target control infusion, propofol, cardiac depression, induction of anesthesia, hemodynamics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- First Affiliated Hospital, Sun Yat-Sen UniversityUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 3 Jan 2013 (estimated)
- Results
- Posted 22 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To compare the hemodynamic changes during anesthesia induction between Marsh and Schnider plasma TCI models. We put forward a hypothesis that, if one TCI model is associated with much more prominent vasodilation effect or cardiac depression, a more sharp decrease in mean arterial pressure, systemic vascular resistance , central venous return or stroke volume would be observed.
Detailed description
Current systems of propofol TCI are pre-programmed with the Marsh and Schnider pharmacokinetic models. Rate constants of Marsh are fixed, whereas compartment volumes and clearances are weight proportional. Schnider model has fixed values for VC, V3, k13, and k31, adjusts V2, k12, and k21 for age, and adjusts k10 according to total weight, lean body mass (LBM), and height. One major benefit of the Schnider model is that it adjusts doses and infusion rates according to patient age. This provides a strong argument for using the Schnider model in the elderly and unwell patients which may improve hemodynamic stability and safety.
However for the vast majority of young and middle age patients, whether Marsh or Schnider would be a better choice for hemodynamic stability remains unknown.
With marsh model, as VC is scaled to body weight, the amount of drug delivered is dependent of body weight. In the Schnider model, as VC at 4.27L is independent of body weight, VC in terms of ml/kg decreases as body weight increases. This and the influence of height and weight on clearance results in heavier patients receiving less propofol on a mg/kg basis whereas those with a lower lean body mass will initially receive about 30% less than delivered by Marsh, but after 30 min, the Schnider model delivers about 15% more. Besides, when Schnider model is used in the morbidly obese, the LBM equation can generate paradoxical values resulting in excessive increases in maintenance infusion rates. Nevertheless, the purpose of this study was to investigate the vast majority of Asian patients whose body weight were in normal range. Only patients with BMI between 18 and 29 were included to minimize the influential factor of body weight in TCI system.
To compare the hemodynamic changes during anesthesia induction between Marsh and Schnider plasma TCI models. We put forward a hypothesis that, if one TCI model is associated with much more prominent vasodilation effect or cardiac depression, a more sharp decrease in mean arterial pressure, systemic vascular resistance , central venous return or stroke volume would be observed.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Marsh | Active comparator | Procedure: Marsh Plasma TCI with high initial targetMarsh Plasma TCI with high initial target |
| Schnider | Active comparator | Procedure: Schnider Plasma TCI with high initial targetSchnider Plasma TCI with high initial target |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Patients between the ages of 18 years and 70 years
- ASA physical status I and II
- surgical procedures requiring general anesthesia with continuous CVP and arterial pressure monitoring.
Key exclusion criteria (7 listed)
- Patients younger than 16 y or older than 65 y
- Body Mass Index (BMI) <18 or >30
- emergency surgery
- allergy to any of the drugs used
- inability to communicate effectively
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 |
|---|---|---|
| Marsh Plasma TCI with high initial targetAlso: Plasma target-controlled infusion in Marsh modelplasma target-controlled infusion in Marsh model(n=30) with an initial target concentration of 4 μg/ml. Target was then reset and gradually titrated to a sedation level with narcotrend index below 64. | Procedure or surgery | Marsh |
| Schnider Plasma TCI with high initial targetAlso: Plasma target-controlled infusion in Schnider modelplasma target-controlled infusion in Schnider model(n=30) with an initial target concentration of 4 μg/ml. Target was then reset and gradually titrated to a sedation level with narcotrend index below 64. | Procedure or surgery | Schnider |
Primary outcome
SVI (Stroke Volume Index) Value Change From Baseline Level at the End of the First 25 Minutes.
Time frame: The end of the first 25 minutes after propofol infusion
After propofol infusion started, according to sedation level, TCI targets were gradually titrated to reach a state of equilibrium at the end of the first 25 minutes. SVI were continuously monitored, at the end of the first 25 minutes, value change from baseline level were calculated.
2 secondary outcomes
NI (Narcotrend Index) Reduction
Time frame: 25 minutes after propofol infusion
CVP (Central Venous Pressure)
Time frame: 25 minutes after induction
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25500489Yang XY, Zhou ZB, Yang L, Zhou X, Niu LJ, Feng X. Hemodynamic responses during induction: comparison of Marsh and Schnider pharmacokinetic models. Int J Clin Pharmacol Ther. 2015 Jan;53(1):32-40. doi: 10.5414/CP202141.
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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.
Xia Feng, M.D. principal investigator
The First Affiliaed Hospital of Sun Yat-sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Marsh Plasma TCI with high initial target and Schnider Plasma TCI with high initial target in people with Healthy, run by First Affiliated Hospital, Sun Yat-Sen University at 1 site in China.
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 3 inclusion and 7 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 29 Mar 2013. 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 China. 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?
Yes. Results are posted in the registry (first posted 22 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
SVI (Stroke Volume Index) Value Change From Baseline Level at the End of the First 25 Minutes. (time frame: The end of the first 25 minutes after propofol infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01759160, which also lists 1 linked publication.
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 29 Mar 2013.