Pharmacokinetic and Other Considerations for Drug Therapy During Targeted Temperature Management.

Abstract

To synthesize an emerging body of literature describing pharmacokinetic alterations and related pharmacodynamic implications affecting drugs commonly used in patients receiving targeted temperature management following cardiac arrest. Peer-reviewed articles indexed in PubMed. A systematic search of the PubMed database for relevant preclinical studies and clinical and observational trials of physiologic changes and drug pharmacokinetic and pharmacodynamic alterations, especially during targeted temperature management/therapeutic hypothermia, but also from cardiac surgery and acute stroke hypothermia models. Detailed review of information contained in published scientific work. Physiologic changes during targeted temperature management significantly alter both the pharmacokinetic and the pharmacodynamic parameters of medications. Current literature describes these alterations and provides practical considerations for management of medications. Medication selection should center on the pharmacokinetics and pharmacodynamics of agents in an attempt to ameliorate potential adverse effects. This review provides an overview of physiologic changes associated with targeted temperature management and practical considerations for the management of medications. Clinicians should understand and anticipate potential drug-therapy interactions of targeted temperature management and mitigate adverse outcomes by appropriate medication selection, dosing, and monitoring. We discuss complications of hypothermia including shivering, electrolyte abnormalities, hemodynamic changes, arrhythmias, and seizures. We review management of these complications as well as considerations for sedation, analgesia, anticoagulation, and prognostication. Approach to interpretation of the clinical significance of drug interactions during targeted temperature management therapy is also addressed.