Stability of Ketamine-Propofol Mixtures for Procedural Sedation

7 Dec
2010

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INTRODUCTION

Procedural sedation and analgesia for painful procedures is the standard of care in emergency medicine. The ideal agent for procedural sedation and analgesia should be safe and easy to administer, should provide analgesia and amnesia with rapid onset, and should allow quick recovery and cause a minimum of adverse effects. Common agents include propofol, ketamine, fentanyl—midazolam, and etomidate.

Ketamine and generic propofol mixed in the same syringe (so-called “ketofol”) has been described as an effective agent for procedural sedation and analgesia in the emergency depart- ment. This combination has also been shown to be safe and effective in the operating room and the office setting and as an induction agent for rapid-sequence intubation in the emergency department. The combination of ketamine and propofol appears to provide sedation and analgesia with fewer toxic effects than either drug alone and with fewer adverse effects than the combination of propofol and fentanyl.
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Future areas of research include the use of different ratios of ketamine and propofol (e.g., 30:70), which may provide greater relaxation while maintaining analgesia and cardiovascular support.

Propofol emulsions are milky white and opaque; when the clear, colourless ketamine solution is added, the admixture takes on the white appearance of the emulsion. Generic propofol emulsions contain soybean oil, glycerin, egg lecithin and water, in addition to 1% propofol. The proprietary brand contains purified egg phosphatide (instead of the egg lecithin) and ethylenediaminetetra-acetic acid (EDTA). The effect of the different formulations on the compatibility and stability of the mixture is not known.

Simulated Y-site administration showed that a 1:1 combination of ketamine and propofol was compatible for 1 h at room temperature. At the time of the current study, there were no reports of the compatibility of ketamine and propofol mixed in a plastic syringe. Therefore, the purpose of the study was to determine the physical compatibility and chemical stability of an extemporaneous mixture of ketamine and propofol when combined in 50:50 and 30:70 proportions and stored in polypropylene syringes at room temperature. Because of the opaque nature of the mixture, precipitation of either compound could not be observed visually; therefore, the concentration changes of both drugs were monitored with high-performance liquid chromatography (HPLC) methods. canadian antibiotics

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