A new four-parameter threshold model for the plasma atracurium concentration-response relationship

Area of Science:

• Anesthesiology
• Pharmacology
• Clinical Pharmacology

Background:

• Atracurium is a neuromuscular blocking agent used in anesthesia.
• Understanding its pharmacodynamics is crucial for safe and effective use.
• Existing models may not fully capture the onset and recovery characteristics.

Purpose of the Study:

• To evaluate the pharmacodynamics of atracurium during and after infusion.
• To assess the fit of a standard pharmacodynamic model to clinical data.
• To investigate a modified model incorporating a threshold effect.

Main Methods:

• Measured plasma concentrations of atracurium and train-of-four (T1:T0) responses in 14 anesthetized patients.
• Fitted a standard biophase pharmacodynamic model to the collected data.
• Compared the standard model's predictions with observed data and tested a threshold model.

Main Results:

• A discrepancy was observed between the predicted and actual onset of neuromuscular depression.
• A modified model including a threshold plasma concentration (CPss theta) improved the data fit.
• CPss theta correlated significantly with CPss50, and model parameter estimates (keo, gamma) differed.

Conclusions:

• A threshold effect may influence the pharmacodynamic response to atracurium.
• The modified model provides a more accurate representation of atracurium's neuromuscular blockade.
• Further research into neuromuscular physiology and modeling is warranted.