LAUSR

Anesthesiology, V 128 • No 5 867 May 2018 I this issue of A NESTHESIOLOGY, Roozekrans et al.1 have revisited the utility function to emphasize the balance between therapeutic efficacy and toxicity of opioids. They reanalyze data from three previously published studies of the analgesic and respiratory depressant effects of alfentanil2–4 to determine “utility” from the perspective of producing analgesia without significant respiratory depression. Further exploration of the theoretical underpinnings of opioid utility is particularly a propos given the escalating number of respiratory depression deaths due to the opioid epidemic5,6 coupled with the most salient finding of the pharmacokinetic–pharmacodynamic analysis of Roozekrans et al.1: that the EC50 for alfentanil analgesia exceeds the EC50 for respiratory depression. This is far from an encouraging therapeutic index. It is, therefore, worth comparing this new work with prior operationalizations of opioid utility while reflecting on how the utility function can evolve and become a more central concept to clinicians, pharmacologists, and public health officials. The Leiden group first introduced the utility function to the anesthesiology literature in 2013.7 This publication prompted an in-depth discussion by Kharasch and Rosow8 of the origins of the utility function and the potential of this important new tool to “intensify the vigor” of the evaluation of the dose-response relationship. The utility function is not a defined equation or computation, but more generally, a determination of value that accounts for both “good” and “bad” outcomes. In its original form the utility function (UF) simplistically computes economic value as: UF profit loss = − Sheiner and Melmon9 translated this into more medical terminology as: