Recent Advances in the Clinical Value and Potential of Dexmedetomidine

Abstract

Dexmedetomidine, a highly selective α2-adrenoceptor agonist, has sedative, anxiolytic, analgesic, sympatholytic, and opioid-sparing properties and induces a unique sedative response which shows an easy transition from sleep to wakefulness, thus allowing a patient to be cooperative and communicative when stimulated. Recent studies indicate several emerging clinical applications via different routes. We review recent data on dexmedetomidine studies, particularly exploring the varying routes of administration, experimental implications, clinical effects, and comparative advantages over other drugs. A search was conducted on the PubMed and Web of Science libraries for recent studies using different combinations of the words "dexmedetomidine", "route of administration", and pharmacological effect. The current routes, pharmacological effects, and application categories of dexmedetomidine are presented. It functions by stimulating pre- and post-synaptic α2-adrenoreceptors within the central nervous system, leading to hyperpolarization of noradrenergic neurons, induction of an inhibitory feedback loop, and reduction of norepinephrine secretion, causing a sympatholytic effect, in addition to its anti-inflammation, sleep induction, bowel recovery, and sore throat reduction effects. Compared with similar α2-adrenoceptor agonists, dexmedetomidine has both pharmacodynamics advantage of a significantly greater α2:α1-adrenoceptor affinity ratio and a pharmacokinetic advantage of having a significantly shorter elimination half-life. In its clinical application, dexmedetomidine has been reported to present a significant number of benefits including safe sedation for various surgical interventions, improvement of intraoperative and postoperative analgesia, sedation for compromised airways without respiratory depression, nephroprotection and stability of hypotensive hemodynamics, reduction of postoperative nausea and vomiting and postoperative shivering incidence, and decrease of intraoperative blood loss. Although the clinical application of dexmedetomidine is promising, it is still limited and further research is required to enhance understanding of its pharmacological properties, patient selection, dosage, and adverse effects.

Keywords: analgesic; anesthesia; anti-inflammation; dexmedetomidine; sedation; surgery.

Figure 1

Routes, procedures, and pharmacological effects of dexmedetomidine. In addition to the intravenous administration of dexmedetomidine, it equally produces sufficient pharmacological outcome through other routes of administration in both surgical and procedural sedation. In its application, dexmedetomidine functions as a sedative, analgesic, adjunct anesthetic/analgesic, and anti-inflammatory agent, among other desirable effects such as bowel recovery and sore throat relief.

Figure 2

The anti-inflammatory effect of dexmedetomidine. Some of the specific mechanisms through which dexmedetomidine reduces inflammation include the inhibited expression of ERK1/2, IL1β, IL6, and TNF, resulting in the polarization of microglia into M2 phenotype and reducing neuroinflammation. Dexmedetomidine also regulates Th1/Th2 cells and their cytokines towards Th1 shift, which causes reduced surgical stress. Moreover, it inhibits inflammatory markers, leading to downregulated immunosuppression capable of mitigating renal injury.

Figure 3

The application of dexmedetomidine in some major surgical procedures. The figure presents a summary of desirable effects exhibited by dexmedetomidine in some selected surgical procedures.