A pharmacogenetic precision medicine approach to analgesia and sedation optimization in critically ill adults

Abstract

Precision medicine is a growing field in critical care. Research increasingly demonstrated pharmacogenomic variability to be an important determinant of analgesic and sedative drug response in the intensive care unit (ICU). Genome‐wide association and candidate gene finding studies suggest analgesic and sedatives tailored to an individual's genetic makeup, environmental adaptations, in addition to several other patient‐ and drug‐related factors, will maximize effectiveness and help mitigate harm. However, the number of pharmacogenetic studies in ICU patients remains small and no prospective studies have been published using pharmacogenomic data to optimize analgesic or sedative therapy in critically ill patients. Current recommendations for treating ICU pain and agitation are based on controlled studies having low external validity, including the failure to consider pharmacogenomic factors affecting response. Use of a precision medicine approach to individualize pharmacotherapy focused on optimizing ICU patient comfort and safety may improve the outcomes of critically ill adults. Additionally, benefits and risks of analgesic and/or sedative therapy in an individual may be informed with large, standardized datasets. The purpose of this review was to describe a precision medicine approach focused on optimizing analgesic and sedative therapy in individual ICU patients to optimize clinical outcomes and reduce safety concerns.

Developing precision‐based multidisciplinary pharmacotherapy management plans in the critically ill

“…For example, a patient's home medication may have been discontinued or replaced with a separate agent. A chronic therapy agent may have been started that is not available to them as an outpatient, or in the case of opioid stewardship, a plan to pull them off should have started the day they were initially prescribed 5 …”

“…One skill in making an adjustment different than the implemented management plan is to state that despite a previous recommendation, a change may be necessary based on new information that is now available. Descriptions of this for fluid/vasoactive agents, pain/sedation/delirium, thrombosis/hemostasis, anticonvulsants or transplantation are provided in other publications in this precision‐based edition 3,5,8–11 …”

“…Patients in the ICU will have various levels of comprehension. Some will be unconscious, sedated, various types of delirium, and others not 5,11 . Nevertheless, there is frequent confusion and uncertainty.…”

Precision medicine in the ICU: One size fits one patient

“…Contributions from an international team of thought leaders and experts provide a detailed overview of ICU topics in a systems-based approach. [1][2][3][4][5][6][7][8] Additionally, original research manuscripts aimed toward optimizing dosing strategies provide valuable insight for bedside clinicians when crafting drug regimens. [9][10][11][12] The vast heterogeneity encountered with ICU patients provides the optimal setting to showcase thevalueofprecisionmedicine.Asclinicians,wemustembracethis step forward to better identify the right therapy for the right patient at the right time.…”

“…This themed edition of Pharmacotherapy is dedicated toward the provision of precision medicine in the ICU. Contributions from an international team of thought leaders and experts provide a detailed overview of ICU topics in a systems‐based approach 1–8 . Additionally, original research manuscripts aimed toward optimizing dosing strategies provide valuable insight for bedside clinicians when crafting drug regimens 9–12 .…”