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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Xia Feng, First Affiliated Hospital, Sun Yat-Sen University
ClinicalTrials.gov Identifier:
NCT01759160
First received: December 20, 2012
Last updated: March 21, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention
Healthy
Procedure: Marsh Plasma TCI with high initial target
Procedure: Schnider Plasma TCI with high initial target

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Diagnostic
Official Title: Hemodynamic Responses During Induction: Comparison of Marsh and Schnider Pharmacokinetic Models in Propofol Plasma Target-controlled Infusion

Resource links provided by NLM:


Further study details as provided by First Affiliated Hospital, Sun Yat-Sen University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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 Outcome Measures:
  • NI (Narcotrend Index) Reduction [ Time Frame: 25 minutes after propofol infusion ] [ Designated as safety issue: No ]
    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) [ Time Frame: 25 minutes after induction ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 60
Study Start Date: December 2012
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Plasma target-controlled infusion in Schnider model

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01759160

Locations
China, Guangdong
The First Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, China, 510080
Sponsors and Collaborators
First Affiliated Hospital, Sun Yat-Sen University
Investigators
Principal Investigator: Xia Feng, M.D. The First Affiliaed Hospital of Sun Yat-sen University
  More Information

No publications provided

Responsible Party: Xia Feng, Department of Anesthesiology, First Affiliated Hospital, Sun Yat-Sen University
ClinicalTrials.gov Identifier: NCT01759160     History of Changes
Other Study ID Numbers: NSFCfengxiar1, Fengxia1
Study First Received: December 20, 2012
Results First Received: January 16, 2013
Last Updated: March 21, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by First Affiliated Hospital, Sun Yat-Sen University:
Target control infusion
propofol
cardiac depression
induction of anesthesia
hemodynamics

ClinicalTrials.gov processed this record on August 19, 2014