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 w
ere associated with histamine release. Nine of 10 volunteers who received e
tomidate in a propylene glycol formulation reported moderate to severe pain
on injection; only one of 10 subjects who received a lipid emulsion formul
ation 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 an
d 0% in the lipid emulsion group (P<0.05). In one volunteer in the propylen
e group, there was a 13-fold increase in histamine concentrations and in on
e subject a four-fold increase. In the lipid emulsion group, no volunteer h
ad an increase in histamine concentrations >1 ng ml(-1). We conclude that e
tomidate formulated in propylene glycol may cause direct injury to vascular
endothelium resulting in pain and venous sequelae, whereas etomidate in li
pid emulsion does not. There was no relationship between pain or venous seq
uelae and histamine release.