Pain, Agitation/Sedation, Delirium, Immobility, Sleep Disruption, and Neuromuscular Blockade

properties; however, studies report that patients who received benzodiazepines in the ICU may maintain

delusional versus factual memories.

Dosing range: 1–4 mg every 4–6 hours intermittent dosing is recommended before using continuous

infusion; accumulation and prolonged awakening times with continuous infusion of lorazepam may

occur because of prolonged duration of action.

Data: Carson et al. studied the number of days on mechanical ventilation in medical ICU patients

receiving intermittent lorazepam (n=64) compared with continuous infusion propofol (n=68); each

group underwent daily interruption of sedation if the fraction of inspired oxygen (Fio2) was less than

80%. Median time on mechanical ventilation was 9 days in the lorazepam group versus 4.4 days in the

propofol group, p=0.006; ICU length of stay was 12.7 days in the lorazepam group versus 8.6 days in

the propofol group (p=0.05); no difference in hospital mortality. Delirium was not assessed in this study

Propylene glycol toxicity: Because of its insolubility, injectable lorazepam is diluted in propylene glycol.

Propylene glycol toxicity can occur with lorazepam infusions for more than 48 hours, particularly

at doses of 6–8 mg/hour or greater, and can manifest as new-onset renal failure, respiratory failure,

metabolic acidosis, and altered mental status. Most hospitals cannot measure quantitative levels of

propylene glycol; therefore, surrogate markers of propylene glycol toxicity such as an elevated osmolar

gap (greater than 10 mOsm/kg) and elevated anion gap with new metabolic acidosis are recommended

for monitoring. If these metabolic abnormalities are present while on a lorazepam infusion, lorazepam

should be discontinued.

Other adverse effects: Paradoxical agitation, confusion, prolonged duration of sedative action,

respiratory depression, hypotension, bradycardia

Pharmacokinetics: Benzodiazepine that binds to the postsynaptic GABAA receptor; undergoes phase

I hepatic metabolism to an active glucuronidated metabolite, α1-hydroxymidazolam, which is then

renally excreted. A short- to medium-acting benzodiazepine in patients with normal renal and hepatic

function. CYP3A4 substrate. Midazolam is highly lipophilic, has a large volume of distribution, and is

highly protein bound.

drug accumulation) or renal (active metabolite α-hydroxymidazolam accumulation) functions are

significantly impaired. Continuous renal replacement therapy partly clears the active metabolite but does

not effectively clear the parent compound and is therefore not recommended as a method for definitive

distribution may lead to significant drug accumulation and a depot effect in the ICU patient. In general,

clearances of midazolam infusions have wide interpatient variability in the ICU, and emergence times

may be significantly prolonged.

Effects: Anxiolysis/sedation, anticonvulsant, muscle relaxant. Maintains anterograde amnesia

properties.

Dosing range: 1–4 mg every 2–4 hours intermittently or as needed should be considered before initiating

continuous infusion. Older adult patients may tolerate only 1–2 mg per dose.