Clinical trial NCT01759160: Hemodynamic Responses During Induction: Comparison of Marsh and Schnider Pharmacokinetic Models
Official title: Hemodynamic Responses During Induction: Comparison of Marsh and Schnider Pharmacokinetic Models in Propofol Plasma Target-controlled Infusion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: Target control infusion
propofol
cardiac depression
induction of anesthesia
hemodynamics
Lead sponsor: First Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2013-01-03
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

Eligibility 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.

Primary outcomes:
measure: SVI (Stroke Volume Index) Value Change From Baseline Level at the End of the First 25 Minutes.
timeFrame: The end of the first 25 minutes after propofol infusion
Secondary outcomes:
measure: NI (Narcotrend Index) Reduction
timeFrame: 25 minutes after propofol infusion
measure: CVP (Central Venous Pressure)
timeFrame: 25 minutes after induction
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: The First Affiliaed Hospital of Sun Yat-sen University
name: Xia Feng, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.