Combination ketamine and propofol for procedural sedation and analgesia

The combination of ketamine and propofol for procedural sedation and analgesia theoretically may be beneficial, with the rationale being that using lower doses of each agent may result in a reduction of the undesirable adverse effects of both agents while maintaining optimal conditions for performing procedures. To examine the current evidence for the efficacy and safety of ketamine and propofol in combination for procedural sedation and analgesia, we searched the MEDLINE (1966-March 2007), EMBASE (1980-March 2007), and Cochrane Database of Systematic Reviews (through the first quarter of 2007) databases for reports describing the use of ketamine and propofol in combination for procedural sedation and analgesia. Additional published reports were identified through a manual search of references from retrieved articles. Prospective, comparative, full-text reports of studies performed in humans that were published in English were reviewed for inclusion. Both authors independently evaluated all studies. Studies in adult and pediatric patients were included if they evaluated efficacy or safety end points. Eight clinical trials were included, seven of which compared a combination of propofol and ketamine with propofol monotherapy. In these trials, variable milligram:milligram ratios of propofol and ketamine were used, ranging from 10:1-2:1, and the optimum dose of these agents in combination is unclear. Combination propofol and ketamine has not demonstrated superior clinical efficacy compared with propofol alone for procedural sedation and analgesia. Conflicting data exist regarding reduced hemodynamic and respiratory complications in patients receiving the combination compared with propofol monotherapy. At higher doses, the addition of ketamine to propofol may incur more adverse effects. Compatibility data for the two agents combined in a syringe are limited. The available evidence does not support the use of a fixed-dose ketamine-propofol combination for procedural sedation and analgesia.