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Safety and efficacy of intramuscular propofol administration in rats
Carolyn M McKune1, Robert J Brosnan, Michael J Dark
1Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Objective:
To determine the safety and efficacy of intramuscularly (IM) injected 100% propofol and propofol-dimethyl sulfoxide (DMSO) mixtures.
Study Design:
Blinded, controlled study.
Animals:
Twenty-five Sprague-Dawley adult female rats weighing 307 +/- 4 g.
Methods:
Three different study protocols were used. In the first set of experiments, rats were injected with 100% propofol (2,6-diisopropylphenol) ranging from 0 to 490 mg kg(-1) into one biceps femoris and equivolume 0.9% saline controls were injected into the contralateral limb. In the second set of experiments, rats were injected with 0 or 262 mg kg(-1) propofol that was dissolved in 10-40% DMSO (by weight); 0.9% saline was used for contralateral limb control injections. In the third experiment protocol, one rat received 293 mg kg(-1) propofol intraperitoneally (IP) to verify potency of the pure compound. Rats were evaluated every 2 minutes for signs of sedation and anesthesia. After 24 hours, all rats were killed, and tissue samples from saline and propofol injection sites were evaluated by veterinary histopathologists who were blinded to drug treatment (propofol versus control) and dose.
Results:
Most rats did not exhibit substantial sedation with IM propofol, and no rat became anesthetized even when propofol was administered in excess of the lethal IP dose. Histology of injection sites demonstrated significant tissue inflammation and necrosis associated with propofol injections, but not with saline injections.
Conclusions And Clinical Relevance:
One hundred percent propofol is neither safe nor effective when administered via the IM route; presumably as a result of poor systemic uptake of the hydrophobic drug. Newer, water-soluble propofol formulations may circumvent these pharmacokinetic problems, yet local tissue injury might still be possible if high concentrations of free propofol drug are liberated.
