Lorazepam (Ativan) is a frequently used sedative in the intensive care unit (ICU). It is a benzodiazepine that can be administered enterally, as intermittent parenteral doses, or as a continuous infusion.
The beneficial effects of lorazepam drip include anterograde amnesia and an opioid-sparing effect via a moderation of the anticipatory pain response.
However, it is not a benign drug and side effects include respiratory depression, tolerance, withdrawal, paradoxical agitation, and prolonged elimination.
One of the carrier molecules of lorazepam is propylene glycol. This has been implicated as the cause of hyperosmolar metabolic acidosis in ICU patients on continuous infusions of lorazepam drip.
About 12% to 45% of propylene glycol is excreted unchanged in the urine, with the remainder metabolized by the liver.
Therefore, caution should be exerted when administering lorazepam drip in patients with renal or hepatic dysfunction. Toxicity from propylene glycol has also been seen with administration of other drugs that use it as a carrier or solvent such as phenytoin, etomidate, nitroglycerin, and diazepam .
Other effects of propylene glycol include renal dysfunction, intravascular hemolysis, cardiac arrhythmias, seizures, and central nervous system (CNS) depression. Fortunately, these metabolic derangements appear to correct after discontinuing the infusion of lorazepam drip.
It is important to note that the upper limit of lorazepam dosing is 0.1 mg/kg/hr, which is about 7 to 10 mg/hr as an infusion for a 70- to 100-kg patient. Each milliliter of lorazepam drip contains about 0.8 mL (830 mg) of propylene glycol, which has a recommended daily allowance of 25 mg/kg/day.
The dose of propylene glycol required for toxicity has not been well established and accumulation has been described over a wide range of lorazepam drip doses.
Also, toxicity has been seen with serum propylene glycol concentrations of 12 to 130 mg/dL and infusion periods ranging from 2 to 24 days. The main factors that appear to be related to toxicity are rate of infusion, length of infusion, and degree of osmolar gap
Alternative sedative drugs to lorazepam include midazolam, propofol, and haloperidol. Because of the side effects and often unpredictable wake-up time associated with benzodiazepines and other sedatives, the agent used should be tailored to each individual patient.