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106

Chapter 8

the simultaneous release of NO from the coronary endothelium after α

2

-stimulation, this

effect is not clinically relevant.

Respiratory

Dexmedetomidine shows no significant effect on hypercapnic or hypoxic respiratory drive

and displays less respiratory depression than other sedatives. However, administration of

opiates, hypnotics, andother sedatives can intensify thepositiveeffects of dexmedetomidine

but also induce negative side effects such as respiratory depression.

Renal

Dexmedetomidine inhibits the release of renin, increases glomerular filtration rate

and excretion of sodium and water, and induces an increased diuresis. It seems that

dexmedetomidine has the potential to reduce perioperatively ischaemia-reperfusion injury.

Gastrointestinal

Α

2

-agonists inhibit the secretion of water and increase the net absorption in the large

intestine. Due to this characteristic, clonidine has even been used in the treatment of

diarrhoea. Production of saliva is also reduced. This can clinically lead to a dry mouth.

Platelets

Α

2

-agonists can – comparable with adrenaline - stimulate the activation of platelets. For that

purpose, a high dose of dexmedetomidine is needed. However, since the normal dosage

of dexmedetomidine decreases the plasma concentration of adrenaline and activates nitric

oxide release, finally a decrease of platelet aggregation is induced.

Applications

ICU

Sedation for ICU patients was the first approved application of dexmedetomidine.

Especially for patients in whom a RASS score of 0 to -3 (mild to moderate sedation) is

pursued, dexmedetomidine has an attractive sedation profile. It provides an adequate level

of sedation, where patients remain arousable to verbal stimulation without respiratory

depression. This enables an easier weaning process and a significantly shorter period of time

to extubation compared with midazolam (3.7 vs. 5.6 days). This was demonstrated in the

SEDCOM study.

7

Patients were treated with a loading dose of 1 μg/kg dexmedetomidine

within 10 min and a continuous maintenance infusion of 1.4 μg/kg/h (EMA approved

dosage) of dexmedetomidine compared with a continuous infusion of midazolam for up