We tested the hypothesis that the
solvent for
etomidate was
a factor in the incidence of
pain and other side effects after injection, and that these were associated with histamine release. Nine of 10 volunteers who received
etomidate in a
propylene glycol formulation reported moderate to severe
pain on injection; only one of 10 subjects who received a
lipid emulsion formulation reported mild
pain (P < 0.05). The incidence of venous sequelae in the injected vein over the next 8 days was 50% in the
propylene glycol group and 0% in the
lipid emulsion group (P < 0.05). In one volunteer in the
propylene group, there was a 13-fold increase in
histamine concentrations and in one subject a four-fold increase. In the
lipid emulsion group, no volunteer had an increase in
histamine concentrations > 1 ng ml-1. We conclude that
etomidate formulated in
propylene glycol may cause direct injury to vascular endothelium resulting in
pain and venous sequelae, whereas
etomidate in
lipid emulsion does not. There was no relationship between
pain or venous sequelae and histamine release.