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DEXMEDETOMIDINE. A SUMMARY
8
INTRODUCTION
The interest in the role of α
2
-agonists in anaesthesia and intensive care has grown
continuously over the past few years. Α
2
-agonists show a wide range of effects including
sedative, anaesthetic-sparing, analgesic, and sympatholytic properties.
In Europe clonidine is often used as pure α
2
-agonist. In America, Asia, the Middle East, Japan,
and Australia dexmedetomidine has been used since 1999 as α
2
-agonist for sedation of
adults in the ICU and during procedural sedations and intraoperative procedures. In June
2011, dexmedetomidine (as Dexdor) was also approved by the European Medicine Agency
(EMA) for sedation of adult ICU patients where it is necessary that sedated patients respond
purposefully to verbal commands.
1-4
Α
2
-agonists
The first α
2
-agonists were sold in the early sixties as spray for nasal congestion. However, this
preparation was quickly taken off the market due to its adverse side effects (hypotension
and prolonged sedation). In 1966, the same agent, now known as clonidine, had a revival as
antihypertensive agent. Over the years, more and more new indications were added, e.g.,
treatment of alcohol and drugs withdrawal, adjuvant medication in myocardial ischaemia,
pain treatment, and intrathecal applications. Dexmedetomidine had been extensively
used in veterinary medicine for sedation and analgesia, before it was registered in 1999 for
sedation in humans.
Pharmacodynamics
A long time, clonidine has been the only α
2
-agonist used in clinical practice. The application
field of α
2
-agonists significantly expandedwith the arrival of dexmedetomidine (Table 1). The
elimination half-life (T
1/2
) of only 2 hours in contrast to clonidine (T
1/2
= 8 hours) contributes
to this development. Dexmedetomidine has a α
1
:α
2
selectivity of 1:1620 compared with
1:220 for clonidine. It is more selective for α
2
A-receptors and has less affinity with the
imidazoline receptor.
3
Bradycardia and hypotension remain - even with dexmedetomidine
- the major side effects. After a bolus of 1 μg/kg dexmedetomidine, blood pressure will
initially rise by activation of the peripheral α
2
B-receptors in the vascular wall. Heart rate will
decline as a reflex. This is more pronounced in younger patients. This first response lasts 5-10
minutes, then blood pressure and heart rate will stabilise 10-20% below the baseline values.
Hypotension and bradycardia seldom require intervention. In patients with a precarious
haemodynamic balance, it is wise to avoid a bolus of dexmedetomidine and to treat the
expectedhypotensionpreventively.Forpatientswithuncontrolledhypotensionoradvanced
AV-block (grade 2 or 3), dexmedetomidine is contraindicated. Compared with clonidine,
the rebound hypertension after abrupt withdrawal of dexmedetomidine is not seen.