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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Procedure: Marsh Plasma TCI with high initial target; Procedure: Schnider Plasma TCI with high initial target

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 Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Marsh; Marsh Plasma TCI with high initial target	Procedure: Marsh 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.; Other Names: Plasma target-controlled infusion in Marsh model
Active Comparator: Schnider; Schnider Plasma TCI with high initial target	Procedure: Schnider 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.; Other Names: Plasma target-controlled infusion in Schnider model

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: First Affiliated Hospital, Sun Yat-Sen University
• Investigators: Principal Investigator: Xia Feng, M.D., The First Affiliaed Hospital of Sun Yat-sen University

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: December 20, 2012
• First Submitted That Met QC Criteria: January 1, 2013
• First Posted (Estimate): January 3, 2013

Study Record Updates

• Last Update Posted (Estimate): March 29, 2013
• Last Update Submitted That Met QC Criteria: March 21, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: hemodynamics; propofol; Target control infusion; cardiac depression; induction of anesthesia
• Other Study ID Numbers: NSFCfengxiar1; Fengxia1 (Other Grant/Funding Number: NSFC3140050)