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.

Effects of dexmedetomidine on patients undergoing radical gastrectomy

“…Although the primary clinical use of dexmedetomidine is mainly for its effects on the central nervous system such as short-term sedation and antianxiety [9], more studies have shown that it can produce organ protective effects against ischemic and hypoxic injuries including cardioprotection, neuroprotection, and renoprotection [10e15]. In animal studies, dexmedetomidine has demonstrated anti-inflammatory effects by reducing the "cytokine storm" to reduce mortality and inhibit inflammatory responses in endotoxemic rats [16e18].…”

Synergistic and additive interactions of the cannabinoid agonist CP55,940 with μ opioid receptor and α2‐adrenoceptor agonists in acute pain models in mice

“…The spinal antinociceptive actions of a 2 -adrenoceptors are mediated mainly by the a 2A -subtype (Jones et al, 1982;Khan et al, 1999;Kamibayashi & Maze, 2000;Malmberg et al, 2001), although a 2C -adrenoceptors also contribute (Fairbanks et al, 2002). Dexmedetomidine is a selective a 2 -adrenoceptor agonist currently approved for clinical use under intensive care conditions (Khan et al, 1999;Coursin & Maccioli, 2001).…”

Effect of dexmedetomidine on the characteristics of bupivacaine in a caudal block in pediatrics

“…It has an a 2 /a 1 selectivity ratio of 1600 : 1, which is eight times more potent than clonidine (200 : 1). 5 DEX has been used effectively in intensive care to aid weaning from mechanical ventilation 6 and is being used increasingly in children. 7,8 However, the use of neuraxial DEX has not been reported before in children.…”