Marsh vs Schnider: Propofol PK Models Compared

The Marsh and Schnider models are the two most widely used pharmacokinetic models for propofol target-controlled infusion. Both describe how propofol distributes through the body using a three-compartment model, but they differ significantly in how they calculate compartment volumes and clearance rates.

Understanding these differences is important because the same target concentration will produce different infusion rates and different bolus doses depending on which model you select.

Marsh Model (1991)

The Marsh model was derived from data published by Marsh and colleagues and became the basis for the Diprifusor, the first commercially available TCI system for propofol.

Key characteristics

• Weight-proportional - all compartment volumes and clearances scale linearly with body weight
• Only uses weight - age, height, and sex do not affect the model parameters
• Fixed rate constants - k10, k12, k13, k21, k31 are the same for every patient
• V1 = 0.228 L/kg - relatively large central compartment
• ke0 variants - classic (0.26 min-1, used in Diprifusor) or modified (1.21 min-1, used in modern pumps)

Because V1 is proportional to weight, the Marsh model predicts larger initial bolus doses for heavier patients. In obese patients, this can lead to excessive dosing because the model assumes that drug distribution scales with total body weight.

Schnider Model (1998/1999)

The Schnider model was developed by Schnider and colleagues using data from 24 volunteers across a range of ages. It was designed to account for the known effects of age and body composition on propofol pharmacokinetics.

Key characteristics

• Multi-variable - uses age, weight, height, and sex to calculate parameters
• Fixed V1 = 4.27 L - small, fixed central compartment (not weight-dependent)
• V2 is age-dependent - older patients have a smaller rapid distribution volume
• Clearance uses lean body mass (LBM) - calculated from height, weight, and sex using the James formula
• ke0 = 0.456 min-1 - fixed value, calibrated to the model

The fixed, small V1 means Schnider gives smaller initial boluses compared to Marsh. This makes induction slower but potentially smoother and safer, especially in elderly or fragile patients.

Side-by-Side Comparison

When to Use Each Model

Choose Marsh when:

• Working with a pump that only supports Marsh (e.g., older Diprifusor-compatible systems)
• Patient is within normal BMI range (18.5-30)
• You want a faster induction due to the larger initial bolus
• You are accustomed to the model and understand its behavior in your patient population

Choose Schnider when:

• Patient is elderly or frail (age-adjusted parameters reduce overdosing risk)
• Patient is obese (BMI > 30), since the model uses lean body mass rather than total weight
• You want a more conservative, smoother induction
• Your pump supports both models and you prefer patient-specific parameter adjustment

Practical Tips

• Never switch models mid-case. The accumulated state from one model is not compatible with another.
• Remember that Schnider at a given Cp target will infuse less drug than Marsh for a heavy patient. Adjust your expectations accordingly.
• For Schnider, always enter accurate height and weight. The LBM calculation is sensitive to these inputs, and extreme values can produce unrealistic parameters.
• For Marsh in patients with BMI over 35, consider using an adjusted body weight instead of actual weight, or switch to Schnider.

References

• Marsh B, White M, Morton N, Kenny GN. Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth. 1991;67(1):41-48.
• Schnider TW, Minto CF, Gambus PL, et al. The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers. Anesthesiology. 1998;88(5):1170-1182.
• Schnider TW, Minto CF, Shafer SL, et al. The influence of age on propofol pharmacodynamics. Anesthesiology. 1999;90(6):1502-1516.