Reduces CBF, CMRO2 and ICP but minimal effect beyond that of sedation Reduces MAP, variable effect on CPP Raises seizure threshold
Pharmacokinetics
Onset of action 2–4 minutes 94% protein bound Highly lipid soluble Hepatic metabolism Renal excretion (some bile) Short context sensitive (2.4 h)
Advantages
Shorter than other benzodiazepines Causes less hypotension than barbiturates or propofol
Disadvantages and major side effects
Metabolites accumulate delaying neurological assessment post cessation of infusion Boluses in TBI reduce MAP (and CPP) Withdrawal syndrome Delirium Respiratory and cough reflex suppression Tachyphylaxis after 72 hours Plateau effect on reducing ICP, where increasing doses have no effect
Dosage
Induction: 0.1 mg/kg Maintenance of sedation: 0.01–0.2 mg/kg/hour
Other significant facts
Interaction with peripheral benzodiazepine leucocyte receptors so may have immunosuppressant effect
Appropriate roles in TBI
Induction of anaesthesia Maintenance of sedation in hypotensive patients with TBI Maintenance of sedation when imminent neurological assessment not required Treatment of seizures
