We discuss propofol infusion syndrome (PRIS) and propylene glycol toxicity from lorazepam infusions, with medical toxicologist Dr. Jerry Snow, director of the toxicology fellowship at Banner University Medical Center in Phoenix.
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Takeaway lessons
* PRIS is a defect in the electron transport chain leading to a failure of ATP production and fatty acid metabolism. There seems to be a susceptibility in some part of the population, but not a clearly understood or monofactorial one. People with mitochondrial disorders are at higher risk, but there is no definitive testing for PRIS risk.
* PRIS has mostly been described with infusions greater than ~67 mcg/kg/min infusions, running for >48 hours.
* The most common presentation is some combination of: elevated lactate, rhabdomyolysis, and new cardiac changes (which may be varied, including new bundle branch block, bradycardia, Brugada-like ST elevations, and changes in function on echo). Trending lactate and CK periodically on high-dose propofol is not a bad idea.
* Triglyceride elevation probably has some association with PRIS, as it is also associated with high propofol doses, but there is not a direct link.
* The primary treatment is stopping propofol and supportive care. There have been some case reports of ECMO being used.
* It is not clear whether patients might be treated by dose-lowering propofol rather than stopping entirely, but it would be a fairly bold move; a safer option might be discontinuation and later rechallenge, but many experts recommend avoiding propofol in the future. Data is limited, but it should probably be added to allergy lists.
* Propylene glycol is a toxic alcohol used as diluent for lorazepam, diazepam, and phenobarbital infusions. It is lower amounts in the latter two, and they are less often used, so toxicity is almost always in lorazepam, and almost always in infusions (not intermittent boluses).
* It is associated with higher infusion rates for prolonged periods. This is probably above >6-7 mg/hr, or >0.1 mg/kg/hr, or >1mg/kg/day, depending on who you ask.
* Propylene glycol is an alcohol, which behaves similarly to other toxic alcohols like ethylene glycol; it creates an elevated osmolar gap, and is metabolized via alcohol dehydrogenase (ADH) to lactate, creating a lactic acidosis.
* Presentation is predominantly an unexplained lactic acidosis. An elevated osmolar gap will help confirm. Mental status can be affected as well. Trending a daily lactate and/or osmolality is not a bad idea on high-dose lorazepam infusions.
* There is no common confirmatory testing, although some centers can probably obtain propylene glycol levels.
* Treatment of propylene glycol toxicity is predominantly stopping or weaning the drip and supportive care. In the most severe cases, it can be treated similarly to other toxic alcohols, including fomepizole and/or renal replacement therapy (especially in patients with renal failure who are more likely to accumulate the compound and its metabolites). It probably does not need to be listed as an allergy/drug reaction.
