Healthy
Conditions
Keywords
Target control infusion, propofol, cardiac depression, induction of anesthesia, hemodynamics
Brief 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 , 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.
Interventions
PROCEDUREMarsh Plasma TCI with high initial target
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.
PROCEDURESchnider Plasma TCI with high initial target
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.
Sponsors
First Affiliated Hospital, Sun Yat-Sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SVI (Stroke Volume Index) Value Change From Baseline Level at the End of the First 25 Minutes. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NI (Narcotrend Index) Reduction | 25 minutes after propofol infusion | Narcotrend was utilized to continuously record patients' sedation level during induction, provided as a criteria for Cpt (Plasma Target Concentration) adjustment. |
| CVP (Central Venous Pressure) | 25 minutes after induction | 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. |
Countries
China
Participant flow
Recruitment details
The recruitment process started from Dec. 2012, ended in Jan.2013. Study location is The First Affiliated Hospital of Sun Yat-sen University.
Pre-assignment details
enrolled participants were excluded when they were found allergic to drugs used during the study.
Participants by arm
| Arm | Count |
|---|---|
| Marsh Plasma TCI in Marsh Model with an initial target of 4 μg/ml, gradually titrated according to sedation level. | 30 |
| Schnider Plasma TCI in Schnider Model with an initial target of 4 μg/ml, gradually titrated according to sedation level. | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Schnider | Marsh | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 30 Participants | 60 Participants |
| Age Continuous | 41.6 years STANDARD_DEVIATION 10.6 | 40.1 years STANDARD_DEVIATION 13.1 | 40.9 years STANDARD_DEVIATION 11.8 |
| Region of Enrollment China | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Male | 15 Participants | 15 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
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.
Time frame: The end of the first 25 minutes after propofol infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Marsh | SVI (Stroke Volume Index) Value Change From Baseline Level at the End of the First 25 Minutes. | -31.1 ml/beat/m^2 | Standard Deviation 9.8 |
| Schnider | SVI (Stroke Volume Index) Value Change From Baseline Level at the End of the First 25 Minutes. | -31.7 ml/beat/m^2 | Standard Deviation 9.9 |
Secondary
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.
Time frame: 25 minutes after induction
Secondary
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.
Time frame: 25 minutes after propofol infusion