Pharmacokinetic and pharmacodynamic properties of dexmedetomidine and its interaction with remifentanil

This dissertation delves into the utilization of dexmedetomidine and its combination with remifentanil in anesthesia. It commences with a literature review and an overview of dexmedetomidine's pharmacokinetic and pharmacodynamic properties. Subsequently, a study is devised, administering escalating concentrations of dexmedetomidine, remifentanil, and a combination thereof to healthy volunteers. Sedation depth is quantified, alongside hemodynamic effects (heart rate, blood pressure, stroke volume, etc.), and blood samples are collected to measure the concentrations of dexmedetomidine and remifentanil in the bloodstream. PKPD modeling is employed to explore the connection between concentrations and response.

The research presented in this dissertation underscores that dexmedetomidine, even when combined with remifentanil, falls short in achieving profound, non-arousable sedation. Nonetheless, dexmedetomidine usage does come with hemodynamic side effects, including a decrease in heart rate and a biphasic influence on blood pressure. Blood pressure decreases at low dexmedetomidine concentrations but rises at higher plasma levels. The addition of remifentanil can mitigate pain without altering sedation levels, but care must be exercised due to a synergistic interaction and an additional reduction in heart rate and blood pressure. Additionally, caution is advised when dealing with high concentrations and extended administration of dexmedetomidine due to nonlinear clearance, which poses the risk of accumulation.

Despite these limitations, dexmedetomidine can prove beneficial in situations demanding patient cooperation, such as craniotomies, colonoscopies, and awake intubations. The pharmacokinetic and pharmacodynamic models elucidated in this dissertation can offer guidance on dosing and safeguard against overdosing.