The drug titration paradox: a control engineering perspective

The drug titration paradox describes that, from a population standpoint, drug doses appear to have a negative correlation with its clinical effect. This paradox is a relatively modern discovery in anesthetic pharmacology derived from large clinical data sets. This review will interpret the paradox using a control engineering perspective.

Drug titration is a challenging endeavor, and the medication delivery systems used in everyday clinical practice, including infusion pumps and vaporizers, typically do not allow for rapid or robust titration of medication being delivered. In addition, clinicians may be reluctant to deviate from a predetermined plan or may be content to manage patients within fixed goal boundaries.

This drug titration paradox describes the constraints of how the average clinician will dose a patient with an unknown clinical response. While our understanding of the paradox is still in its infancy, it remains unclear how alternative dosing schemes, such as through automation, may exceed the boundaries of the paradox and potentially affect its conclusions.