Dexmedetomidine in Paediatric Anaesthesia
Highlights
- Dexmedetomidine (DEX) is a highly selective α2-agonist that provides sedation which parallels natural sleep, anxiolysis, sympatholysis and an anaesthetic-sparing effect without clinically significant respiratory depression (View Highlight)
- It produces this sedative effect via α2 adrenoceptors in the locus coeruleus in the central nervous system. A single intraoperative dose without a subsequent infusion has been shown to reduce postoperative analgesic requirements, provide smoother emergence from anaesthesia and prolong regional anaesthesia. (View Highlight)
- Dexmedetomidine is a highly lipophilic drug with a high volume of distribution (VD) in both children and adults. (View Highlight)
- Dexmedetomidine is predominantly bound to plasma proteins, primarily albumin and α1 glycoprotein (View Highlight)
- It readily crosses and blood brain barrier and has a VD in children older than 1 yr similar to adult values (View Highlight)
- It is thought to fit a two-compartment model with first order elimination. (View Highlight)
- Dexmedetomidine is broken down by the hepatic enzymes uridine 5′-diphospho-glucuronosyl-transferase and cytochrome P450 (CYP2A6) to inactive metabolites and direct glucuronidation, which are excreted in bile and through renal pathways. (View Highlight)
- Pharmacokinetic studies in adults show that DEX is rapidly distributed and has a short elimination half-life of 2.0 h (View Highlight)
- Clearance in neonates (42.4% of adult values, reaching 84.4% by 1 yr old) and infants is reduced, owing to immaturity of elimination pathways (View Highlight)
- The maturation parameters for clearance are closely related to morphine maturation (View Highlight)
- Transient DEX-induced hypertension appears to occur more frequently with repeated large boluses of 2–3 μg kg−1 and more likely to occur in infants than in older children. (View Highlight)
- bradycardia of up to 30% from baseline should be expected with the use of DEX in children (View Highlight)
- The use of anticholinergics to treat bradycardia resulting from DEX administration should be done with caution as there are even reports of profound transient hypertension when glycopyrrolate is used to treat DEX-induced bradycardia (View Highlight)
- The bioavailability of nasal (40.7%) and buccal (81%) DEX has been shown to differ quite markedly.7 Oral bioavailability is very poor (16%) (View Highlight)
- I.N. DEX does not have the nasal irritation that is common with giving i.n. midazolam. The irritation can lead to poor drug effectiveness because of the associated coughing and sneezing (View Highlight)
- I.N. DEX has the additional benefit of reduced postoperative nausea and vomiting and need for rescue analgesics.12 The mechanism of action of its antiemetic effect is via decreased dopamine levels in the locus coeruleus and its analgesic effect, thereby reducing the need for opioids (View Highlight)