By reducing the concentration of propofol in the aqueous phase with intrapipid injection, the pain during injection was alleviated. Doenicke et al. hypothesized that the concentration of propofol in the aqueous phase may be an important variable of pain induced by propofol injection.
They note that the results of the in vitro study showed a relatively high concentration of propofol in the aqueous phase of Diprivan (18.57 mg/ mli1), suggesting that the active ingredient was not completely dissolved in the lipid carrier. In propofol emulsion, the distribution of the drug is different between the two phases, there is an outer aqueous phase and an inner lipid phase.
During injection, only the outer aqueous phase makes contact with the vein lining. The concentration of the irritant in the aqueous phase may be a factor causing venous pain at the time of administration. Propofol, like all phenols, can irritate the skin and mucous membranes. Therefore, mass injections of propofol preparations may cause pain. They went on to show that the incidence of pain caused by propofol injections could be reduced by increasing the lipid content of propofol and thus reducing the concentration of propofol in the water phase. Clinical strategies for preventing pain from propofol injections Based on the proposed mechanisms and factors associated with pain from propofol injections, several methods for preventing pain have been tried with varying degrees of success. Published studies have produced mixed results, in part because of differences in methodology.
Methods studied to date include: injection site, use of aspirin and other NSaids, pre-administration, injection rate, carrier intravenous infusion rate, use of local anesthetics, dilution of propofol, different temperatures, opioids, metoclopramide, triglyceride trinitrate, thiopentone, ketamine, different syringe materials, and blood aspiration. There was a significant association between injection site and incidence of injection pain when Cremophor EL was used at injection site.