Minnesota Anesthesia Services

Ketamine-Propofol in Combination

Many procedures require sedation and analgesiaranging from electric cardioversion, to closed reduction of orthopedic injuries, to abscess incision and drainage, and to gastrointestinal endoscopy (1). An appropriate agent for procedural sedation should provide consistent and predictable effect, rapid onset, brief recovery time, and few complications. However, as no single drug can provide all of these benefits, a combination of different sedative, analgesic, or dissociative agents often needs to be considered (1). Ketamine and propofol in combination is one such option.

Propofol is a sedative/hypnotic that is frequently used for procedural sedation and offers several advantages compared to other pharmacologic agents, including ease of titration, rapid onset of action, and brief duration of effect. However, propofol may cause dose-dependent adverse events such as respiratory depression and hemodynamic instability (shock). Although propofol has some amnestic and antiemetic properties, it is not an analgesic, so opioids and other agents, such as ketamine, are often used in combination to provide pain control (2).

Ketamine is a phencyclidine derivative with dissociative, sedative, and analgesic properties that preserves muscle tone and protects airway reflexes and spontaneous respiration. Pretreatment with ketamine has proved effective in preventing propofol infusion pain, and counteracts the hemodynamic depression of propofol. When prescribed alone, side effects such as emergence phenomena, postoperative dysphoria, vomiting, or laryngospasm can be seen. The combination of ketamine plus propofol, with opposing hemodynamic and respiratory effects, leads to use of smaller doses of each one and results in diminished dose-dependent side effects (3).

In a study published in the Journal of Academic Emergency Medicine, Nejati et al. performed a prospective randomized controlled trial (RCT) involving emergency department patients requiring procedural sedation to compare the efficacy of the ketamine/propofol with midazolam/fentanyl (the standard for procedural sedation at certain medical centers) (2). 62 patients scheduled for procedural sedation who presented between January 2009 and June 2009 were enrolled prospectively. 31 were randomly assigned to the ketamine/propofol (ketofol) group and 31 were assigned to the midazolam/fentanyl (MF) group.

The median administered dose of ketofol was 1.125 mg/kg for propofol and 1.125 mg/kg for ketamine. In the MF group, the median doses of midazolam and fentanyl were 0.04mg/kg and 2 μg/kg, respectively (2). It was found that perceived pain, as measured by the Visual Analogue Scale (VAS), was significantly lower in the ketofol group than the MF group (median ketofol = 0, vs. median MF = 3, p<0.001). Additionally, only 1 (3.2%) of the ketofol patients experienced a significant decrease in oxygen saturation (SpO2 < 92%), compared to 11 (35.5%) of the MF patients (p = 0.003).

Based on these results, it can be concluded that co-administration of propofol and ketamine provided a deeper level of sedation and analgesia with less oxygen desaturation compared to the combination of midazolam and fentanyl (2). However, there were more adverse events in the group treated with both propofol and ketamine. For example, 9 patients (29%) in the ketofol group experienced agitation upon emergence and 4 (12.9%) experienced involuntary movements. Neither of these side effects were observed in the MF group. Interestingly, the authors of the study note that providing a low dose of midazolam as pretreatment before administration of ketofol can increase both physician and patient satisfaction by reducing clonic movements and emergence phenomenon during and after induction, while preserving the superior sedative effects of ketofol (2).

References

1. Slavik VC, Zed PJ. Combination ketamine and propofol for procedural sedation and analgesia. Pharmacotherapy. 2007;27(11):1588-1598. doi:10.1592/phco.27.11.1588

2. Nejati A, Moharari RS, Ashraf H, Labaf A, Golshani K. Ketamine/propofol versus midazolam/fentanyl for procedural sedation and analgesia in the emergency department: a randomized, prospective, double-blind trial. Acad Emerg Med. 2011;18(8):800-806. doi:10.1111/j.1553-2712.2011.01133.x

3. Yan JW, McLeod SL, Iansavitchene A. Ketamine-Propofol Versus Propofol Alone for Procedural Sedation in the Emergency Department: A Systematic Review and Meta-analysis. Acad Emerg Med. 2015;22(9):1003-1013. doi:10.1111/acem.12737