Optimal infusion policy of intravenous morphine and ketamine - A Mixed-Integer Linear Programming application

Area of Science:

• Pharmacology and Pharmacokinetics
• Control Systems Engineering
• Computational Medicine

Background:

• A novel model for drug interactions, including side effects, has been introduced.
• This model identifies an optimal effect compartment concentration range for maximizing patient well-being.
• This target range guides optimal drug infusion strategies.

Purpose of the Study:

• To apply the novel drug interaction model to the combination of intravenous morphine and ketamine.
• To identify the optimal concentration range for this drug combination.
• To design a controller for optimizing drug infusion based on this range.

Main Methods:

• Application of a recently proposed drug interaction and side effect model.
• Identification of the optimal effect compartment concentration range for morphine and ketamine.
• Formulation and solution of a mixed continuous-discrete optimal control problem.
• Controller design using the center of the optimal range as a reference value.

Main Results:

• The optimal concentration range for intravenous morphine and ketamine was identified.
• The center of this optimal range was determined for controller design.
• An optimal infusion policy was derived, minimizing overall drug consumption.

Conclusions:

• The novel model effectively identifies optimal therapeutic ranges for drug combinations.
• Optimized drug infusion policies can be designed to enhance patient well-being and reduce drug usage.
• This approach holds promise for personalized medicine and improved clinical outcomes.