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[q unit=”Pharmacology” topic=”Dexmedetomidine”] Rationale for Dexmedetomidine

[a] Sedation practice varies widely around the world. Propofol and Midazolam are the mainstays of sedation, in addition to an opiate as an antitussive.

Traditional first line agents act mainly via GABA.

Dexmedetomidine is an alpha-2 agonist administered by continuous infusion. It facilitates conscious sedation and delivers analgesia.

Experiemental evidence suggests possible protective effects against neuronal, myocardial and renal injury. Similarly it has been shown to reduce inflammation in sepsis (with reduced delirium and mortality) as well as post cardiopulmonary bypass.

Some evidence exists that dexmedetomidine may potentiate hypoxic pulmonary vasoconstriction thereby protecting against shunt.

[q unit=”Pharmacology” topic=”Dexmedetomidine”] Advantages of Dexmedetomidine

[a] Analgesic and sedative properties.

Conscious sedation facilitates improved communication and participation in PT/OT etc.

Possible anti-inflammatory properties.

May preserve Hypoxic Pulmonary Vasoconstriction.

Titratable.

Can be used safely in non-ventilated patients when appropriately monitored.

[q unit=”Pharmacology” topic=”Dexmedetomidine”] Disadvantages of Dexmedetomidine

[a] Cost – though this is improving

Common usage strategies are technically ‘off label’ (>24h, >0.7mcg/kg/h, non-vent, etc)

Bradycardia including asystole

Hypotension

Colonic pseudo-obstruction (Ogilvie’s Syndrome)

Cannot bolus to rapidly re-sedate (though commenced via bolus in anaesthesia setting)

[q unit=”Pharmacology” topic=”Dexmedetomidine”] Evidence for Dexmedetomidine

[a] MIDEX-PRODEX 2012
– non-inferior to midazolam

SPICE 2012
– early deep sedation worsened time to extubation, time to delirium, and 180d mortality

SPICE 2013
– same, in other ICUs

DahLIA 2016
– more ventilator free hours at day 7

Shrobik 2018
– more patients delirium free

SPICE3 2019 *** a big one, n=4000, NEJM
– no mortality benefit
– 1 more ventilator free day
– possible mortality benefit in elderly (–> SPICE4)

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