Thanks to Dr. RW – Propylene glycol toxicity due to high dose lorazepam infusions
ADR Prevent-ERR: IV Lorazepam Infusion and Propylene Glycol Toxicity
A hospitalized patient with respiratory failure was sedated for intubation with a continuous infusion of lorazepam, initially running at 4 mg/hour but increased over the next several days to a maximum rate of 8 mg/hour (716 mg cumulative dose). The patient’s baseline chemistries were within normal limits but deteriorated over the next several days. The patient then developed acute renal failure with a metabolic acidosis and an elevated osmolal gap of 90 mOsm/L (normal is 10 to 15 mOsm/L). The patient’s BUN rose from 15 to 84 mg/dL and his serum creatinine increased from 1.0 to 3.7 mg/dL. The physician suspected that the patient’s subsequent renal insufficiency and acute tubular necrosis were due to propylene glycol toxicity secondary to the continuous lorazepam infusion. The patient’s propylene glycol level was 37 mg/dL (greater than 18 mg/dL is toxic). Bicarbonate infusions were initiated and the sedating agent was changed to midazolam. Resolution of the acidosis and renal failure subsequently occurred within 5 days.
When I teach increased anion gap acidosis, I use the initials KILU.
K – Ketoacidosis – DKA, alcoholic ketoacidosis and starvation ketosis
I – Ingestions – primarily ethylene glycol, methanol and salicylates – althought rarely iron or INH
L – Lactic acidosis – most common from anerobic metabolism due to underperfused tissues. Classic examples includes shock, dead bowel, dead limbs. Some tumors can chronically secrete lactic acid (I once was given a CPC with this diagnosis). You must always consider drugs – metformin can, but the rate is generally overestimated, and Didanosine (an antiretroviral drug).
Finally we have two causes of D-lactic acidosis. You have to order D-lactic acid levels specifically to make these diagnoses, since their routine lactic acid levels are normal. D-lactic acidosis secondary to short bowel syndrome –
D-lactic acid found in human physiological fluids originates from bacterial production in the intestinal tract, from D-lactate ingestion, or from endogenous production by the methylglyoxylase pathway.
The complication of IV lorazepam (Ativan) includes D-lactic acidosis. This article, which Dr. RW posted on his web site, describes the entire syndrome well. For those who ever care for patients receiving IV lorazepam, this complication should be anticipated.
U – uremia – rarely causes a major anion gap acidosis.
Most physicians are not aware of this unusual complication. We often consider drug side effects. This complication is a diluent side effect. Fortunately, patients respond to stoppin the infusion (and replacing its actions with another medication).
