A common misconception regarding benzodiazepines used in the intensive care unit (ICU) is that they are interchangeable agents producing the same effects. This approach does not acknowledge the pharmacologic differences between midazolam and lorazepam, which is primarily in their lipophilic properties. Lipophilicity directly affects the onset and duration of action of a drug. In addition, it is important to note that the pharmacokinetics of each drug changes considerably when they are given as a single bolus versus an infusion.

As a single bolus, midazolam has a shorter onset and duration of action than lorazepam, which makes it optimal for acute agitation or sedation prior to a procedure. The reason is that midazolam undergoes a transformation to a highly lipid state after administration. The highly lipophilic benzodiazepines, such as midazolam and diazepam, are able to cross the blood–brain barrier rapidly, causing a quick onset of action; midazolam has an onset of action of 0.5 to 5 minutes. In contrast, lorazepam is less lipophilic, which delays the crossover into the blood– brain barrier after a single bolus; lorazepam has an onset of action of 15 to 20 minutes. Being highly lipophilic also results in short duration of action after a single bolus. Agents like midazolam are able to readily leave the central nervous system (CNS) and move back into the plasma compartment (midazolam duration is 2 hours), whereas the more polar lorazepam is trapped in the CNS, resulting in a longer duration of action (6 to 10 hours).