"improving intensive care in Scotland"

Benzodiazepines

  • Benzodiazepines are commonly used sedatives in ICU, the most common being midazolam and diazepam and occasionally lorazepam.

  • Benzodiazepines act via benzodiazepine receptors which produce their effect through GABA-mediated inhibition within the central nervous system.

  • All three agents can produce sedationhypnosisanxyiolysisanterograde amnesiamuscle relaxation and are anti-epileptic.

  • There is marked inter-patient variability and tolerance with benzodiazepines requiring individual titration.

  • These three benzodiazepines can also produce hypotension in haemodynamically unstable patients, and hypoventilation in spontaneously breathing patients. Again great care is required with their use, with appropriate monitoring and rescue therapies immediately available.

  • Paradoxical agitation may also occur during light sedation, thought to be caused by drug-induced amnesia or disorientation.

  • All three accumulate when administered by infusion.

Midazolam

  • Midazolam is generally made up into a 1mg/ml solution and run between 1 and 10mls/hr with titration to a pre-determined end point.

  • Midazolam has a rapid onset (0.5-2.5 mins) and a reasonably rapid offset (30 to 60 mins) of action. It therefore tends to be given by infusion.

  • Minimal accumulation occurs with short infusions (< 24hours) but is seen thereafter.

Diazepam

  • Diazepam is administered both intravenously and enterally.

  • Diazepam has both a very long terminal elimination half-life and active metabolites. As a result of this it is only really administered intermittently to minimise accumulation.

  • It is generally administered in doses of approximately 0.5-5mg intravenously and 2-10mg enterally.

  • Intravenously diazepam has a reasonably rapid onset of action (within 2-3 mins) with repeat doses every 2-4 hours.

  • Enterally diazepam takes approximately 30-60 minutes for onset of action with further doses every 6-8 hours.

Lorazepam

  • Lorazepam is administered both by infusion (1-7mg/hr) and intermittently (1-4mg).

  • It has a slow onset of action (approx. 5mins) and a long duration of action (6-10hours) making it less titratable.

  • However, lorazepam's wake-up has been found to be more predictable than midazolam's with prolonged infusion thus the reason it is favoured by some for prolonged infusion. The reasons for this are: lorazepam's metabolism is less influenced by other factors (e.g. drugs), its metabolites are inactive and it has a more stable context-sensitive half time.

  • It comes prepared in polyethylene glycol and propylene glycol which are thought to be the cause of a very rare disorder characterised by a hyperosmolar, lactate acidaemia with acute tubular necrosis associated with prolonged, very high-dose lorazepam infusion.

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