Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Dexmedetomidine

Precedex (Abbott)
2 mL ampoules containing 100 microgram/mL
Approved indication: sedation
Australian Medicines Handbook Section 2.2

For several years it has been known that the antihypertensive drug clonidine can reduce the required dose of anaesthetic drugs. It does this by stimulating alpha2 adrenoceptors. Dexmedetomidine also acts as an agonist at these receptors. This action has analgesic effects and, possibly because of an effect on the locus ceruleus, also causes sedation.

Dexmedetomidine has been approved for the sedation of intubated post-surgical patients during treatment in intensive care. It has been compared with placebo for this indication in a British study. Patients who were given dexmedetomidine required 80% less midazolam for sedation and 50% less morphine for analgesia.1 A study comparing dexmedetomidine with propofol found that both drugs adequately sedated the patients. Those given dexmedetomidine required significantly less morphine for analgesia. Dexmedetomidine has an advantage because it causes little respiratory depression, so patients can be extubated without having to wait for their respiratory function to recover.

As dexmedetomidine is given by infusion, it must be diluted before use. A loading dose is given over 10 minutes followed by a maintenance infusion which is adjusted according to the clinical response. The infusion should not exceed 24 hours.

Dexmedetomidine has a half-life of two hours. It is almost completely metabolised with most of the metabolites being excreted in the urine. Dose reductions maybe needed for patients with renal or hepatic impairment. Although cytochromeP450 2A6 is involved in the metabolism clinically significant interactions are thought to be unlikely.

Dexmedetomidine does interact with anaesthetic drugs, opioids and sedatives so it should only be used in intensive care. Patients require monitoring of their electrocardiogram, oxygen saturation and blood pressure.

Hypotension is the most common adverse reaction, occurring in 22% of patients, however some patients will become hypertensive. Dexmedetomidine can also cause bradycardia. Patients who are elderly, or who have diabetes or heart failure, have an increased risk of these adverse effects because of changes in their autonomic nervous systems. Lower doses are recommended for the elderly.

Dexmedetomidine has been approved on the evidence gathered from fewer than600 patients. It may take more clinical experience to determine whether its benefits are outweighed by the adverse reactions.

References

  1. Venn RM, Bradshaw CJ, Spencer R, Brealey D, Caudwell E, Naughton C. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia 1999;54:1136-42. .