Hemodynamic Responses During Induction: Comparison of Marsh and Schnider Pharmacokinetic Models

Study Overview
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Brief Summary
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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
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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.

Official Title
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Hemodynamic Responses During Induction: Comparison of Marsh and Schnider Pharmacokinetic Models in Propofol Plasma Target-controlled Infusion

Conditions
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Healthy

Intervention / Treatment
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* Procedure: Marsh Plasma TCI with high initial target
* Procedure: Schnider Plasma TCI with high initial target


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Marsh<br>Marsh Plasma TCI with high initial target | Procedure: Marsh Plasma TCI with high initial target<br>* 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.<br>* Other names: Plasma target-controlled infusion in Marsh model;|
| Active Comparator: Schnider<br>Schnider Plasma TCI with high initial target | Procedure: Schnider Plasma TCI with high initial target<br>* 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.<br>* Other names: Plasma target-controlled infusion in Schnider model;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | The end of the first 25 minutes after propofol infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 25 minutes after induction | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Target control infusion, propofol, cardiac depression, induction of anesthesia, hemodynamics