Haugen et al. found that pretreatment with 50 mg of thiopental did not reduce morbidity, but did reduce the severity of pain. The differences between the two studies may be due to the different doses of thiopental and lidocaine used and the different rates of injection of propofol. Lee used 100 milligrams of sodium thiopental, which can affect adequate pain assessment, while Haugen used only 50 milligrams of sodium thiopental.

Lee studied a group of patients given 20 mg of lidocaine, and Haugen studied a group given 40 mg of lidocaine. Lee was given 4 ml of propofol within 4-8 s, while Haugen was given 1 mg·kg·1·min·1. Ketamine Tan et al. found that pretreatment with 10 mg of ketamine in normal saline 30 s before propofol injection could significantly reduce the incidence of pain during propofol injection from 84% to 26%. They speculate that this mechanism is the result of the effect of peripheral local anesthesia, which attenuates the afferent pain pathway, rather than the central analgesic effect due to the lower dose used (0.2 mg.kgi1). Manufacturers of the syringe material propofol have demonstrated that it can remove silicone lubricant from single-use plastic syringes.

Lomax believed that the pain of propofol injection was due to irritating substances produced when propofol was in contact with disposable plastic syringes. He went on to point out that when glass syringes were used instead of plastic syringes, the incidence of pain caused by propofol injections could be significantly reduced from 33% to 16%.

Blood suction McDonald and Jameson conducted a study on the buffering effect of blood in reducing pain associated with propofol injection. They found that inhaling 2 ml of a patient's blood into a propofol syringe immediately before injection was more effective in reducing pain than adding 2 ml of saline to propofol, and that the technique was no more effective than adding 20 mg of lidocaine to propofol (saline: 58%, blood: 13%, lidocaine: 18%). They suggested that the blood might alter the concentration of propofol's free aqueous solution, or that the initial release of propofol to kinin could be reduced by initially injecting the blood back into the patient. Conclusion The cause of pain caused by intravenous propofol and other drugs is still unclear.

Although several mechanisms for pain from propofol injections have been proposed, they are not based on any hard physiological data. A number of approaches have been tried to reduce the incidence and severity of pain from propofol injections, but with varying success. This may indicate that multiple mechanisms, receptors or factors are involved. Further research is needed in this area.

Currently, the wise choice is to use a combination of techniques such as afentanil preconditioning, mixing lidocaine with propofol, and injecting large vein without carrier fluid to reduce the incidence and severity of propofol injection pain.