Philip E. Empey

Learn More
The clinical use of therapeutic hypothermia has been rapidly expanding due to evidence of neuroprotection. However, the effect of hypothermia on specific pathways of drug elimination in humans is relatively unknown. To gain insight into the potential effects of hypothermia on drug metabolism and disposition, we evaluated the pharmacokinetics of midazolam as(More)
OBJECTIVES Therapeutic hypothermia is widely employed for neuroprotection after cardiac arrest. However, concern regarding elevated drug concentrations during hypothermia and increased adverse drug reaction risk complicates concurrent pharmacotherapy. Many commonly used medications in critically ill patients rely on the cytochrome P450 3A isoform for their(More)
BACKGROUND AND PURPOSE Reducing body temperature can prolong tolerance to ischemic injury such as stroke or myocardial infarction, but is difficult and uncomfortable in awake patients because of shivering. We tested the efficacy and safety of the alpha-2-adrenergic agonist dexmedetomidine for suppressing shivering induced by a rapid infusion of cold(More)
Genetic knockout mice studies suggested ATP-binding cassette transporter family G member 2 (ABCG2)/Abcg2 translocates nitrofurantoin at the mammary-blood barrier, resulting in drug accumulation in milk. The purpose of this study was to establish the role of Abcg2 in nitrofurantoin accumulation in rat milk using(More)
BACKGROUND This study sought to evaluate the efficacy of lipid emulsion in reversing bupivacaine-induced cardiovascular collapse when added to a resuscitation protocol that included the use of epinephrine and vasopressin. METHODS After induction of general anesthesia and instrumentation, 19 mixed-breed domestic swine had cardiovascular collapse induced by(More)
Operation Brain Trauma Therapy (OBTT) is a consortium of investigators using multiple pre-clinical models of traumatic brain injury (TBI) to bring acute therapies to clinical trials. To screen therapies, we used three rat models (parasagittal fluid percussion injury [FPI], controlled cortical impact [CCI], and penetrating ballistic-like brain injury(More)
Although the precise mechanism of action remains to be defined, Cyclosporin A (CsA) has demonstrated potential for neuroprotection in animal models. Predictive dosing strategies for CsA in acute traumatic brain injured (TBI) patients must account for the influence of the acute phase response on drug disposition. To characterize CsA pharmacokinetic(More)
OBJECT Cyclosporine neuroprotection has been reported in brain injury models but safety and dosing guidelines have not been determined in humans with severe traumatic brain injury (TBI). The purpose of this investigation was to establish the safety of cyclosporine using 4 clinically relevant dosing schemes. METHODS The authors performed a prospective,(More)
Severe pediatric traumatic brain injury (TBI) is associated with unfavorable outcomes secondary to injury from activation of the inflammatory cascade, the release of excitotoxic neurotransmitters, and changes in the reactivity of cerebral vessels, causing ischemia. Hypoperfusion of injured brain tissues after TBI is also associated with unfavorable(More)
Mild therapeutic hypothermia is emerging clinically as a neuroprotection therapy for individuals experiencing cardiac arrest (CA); however, its effects combined with disease pathogenesis on drug disposition and response have not been fully elucidated. We determined the activities of four major hepatic-metabolizing enzymes (CYP3A, CYP2C, CYP2D, and CYP2E)(More)