Dexmedetomidine.

Abstract

Effective use of sedative-hypnotic and analgesic agents is an integral part of providing patient comfort and safety. Of the numerous drugs administered, benzodiazepines, propofol, and narcotics are the most popular. Even these proven, time-tested sedative-hypnotics and analgesics are not perfect, however, and modern intensive care demands a more ideal product. The development of dexmedetomidine, an alpha2-agonist, is an attempt to improve sedative/analgesic use and provide a drug that possesses the characteristics outlined in Table 1. It stimulates alpha2-adrenergic receptors in the locus ceruleus to provide sedation and in the spinal cord to enhance analgesia. It also causes sympatholysis via central and peripheral mechanisms. Dexmedetomidine binds alpha2-receptors eight times more avidly than clonidine and is shorter acting. It was initially evaluated as an anesthetic, but was associated with excessive bradycardia and hypertension, followed by hypotension. In late 1999, dexmedetomidine was approved for adult ICU use for less than 24 hours as a sedative infusion. It currently lacks approval in Europe. Most of the clinical experience with dexmedetomidine has been with surgical patients undergoing cardiac and vascular procedures. Careful patient selection and proper drug infusion are needed to avoid excessive deleterious hemodynamic results. Slower bolus loading over 20 minutes results in minimally decreased heart rate and blood pressure. Continuous infusion maintains unique sedation (patients appear to be asleep, but are readily roused), analgesic sparing effect, and minimal depression of respiratory drive. More experience with dexmedetomidine infusion in medical ICU patients and patients with complex end-organ dysfunction such as respiratory failure or systemic inflammatory response syndrome is needed before conclusions can be drawn about the drug's potential for wider application and its long-term (> 24 h) safety and effectiveness.