The POKER Trial: Go All in on Ketofol?

Background: Procedural sedation and analgesia is a frequently performed procedure in the emergency department to help facilitate care of patients in an effective manner. Our goal should be to minimize pain and anxiety while minimizing adverse effects. We have discussed the complications associated with procedural sedation and analgesia on REBEL EM before HERE.  Ketamine and Propofol are two agents commonly used for this and each agent has its own theoretical advantages and disadvantages. Due to this, it has been hypothesized that the combination of the two agents may result in fewer adverse events because of each agent counteracting the disadvantages of the other. Despite this, to date, no RCTs have really shown a reduction in adverse events with the combination of propofol and ketamine.

What Article are we Discussing:

  1. Ferguson I et al. Propofol or Ketofol for Procedural Sedation and Analgesia in Emergency Medicine – The POKER Study: A Randomized Double-Blind Clinical Trial. Ann Emerg Med 2016 [Epub Ahead of Print] PMID: 27460905

What They Did:

  • Multicenter, Randomized Double-Blind Trial of adult patients requiring deep sedation
  • Randomized to 1:1 ketofol vs propofol
  • ≥18 years of age requiring deep procedural sedation
  • Excluded if allergy to ketamine, soy products or eggs


  • Primary: Occurrence of respiratory adverse event requiring an intervention
    • Desaturation SpO2≤93%
    • Apnea = No Capnography Trace for ≥15seconds
    • Hypoventilation = RR ≤8 breaths/min
    • Laryngospasm
    • Aspiration = Persistent hypoxia plus infiltrates on CXR
  • Secondary:
    • Hypotension SBP <90mmHg
    • Patient Satisfaction




  • Sedating physician, Procedural physician, Registered nurse, and patient were all blinded to contents of “study drug” syringes used
  • Data available on primary outcome on all patients enrolled
  • Largest study to compare ketofol in a 1:1 ratio in a single syringe with equivalent volumes of 1% propofol for ED procedural sedation and analgesia


  • Convenience sample which could lead to a selection bias
  • There was no control for prophylactic oxygen delivery or pre-procedural opiate use, which could have introduced confounders into the study.
  • Use of a combined physiologic and intervention-based outcome measure is not an objective outcome. Different physicians will have different triggers that cause them to intervene. (i.e. The physiologic parameters are objective however physician intervention is subjective. )
  • Australian studies on satisfaction may differ from US satisfaction


  • This study was powered to demonstrate a reduction in the primary endpoint by 20 – 10%
  • Hypotension occurred more often in the propofol arm vs the ketofol arm (8% vs 1% respectively). This was a statistically significant finding, however the clinical significance of this is questionable at best, as most patients hypotension was self limiting with only a few requiring a fluid bolus
  • Although pain scores at 30 minutes post procedure were lower in the ketofol group, this did not affect patient satisfaction
  • Labeling syringes with different medications, plus keeping track of how much of what medication you have given, seems to add additional math and the potential for more complications with dosing of ketofol, when there really hasn’t been any major improvements in patient oriented outcomes
  • There have been 2 other studies that have compared propofol to ketofol for procedural sedation and analgesia:
    • Andolfatto G et al 2012: Randomized, double-blind trial of ketofol vs propofol of 284 patients with a primary outcome of adverse respiratory events. Adverse respiratory events were experienced in 30% of patients receiving ketofol and 32% in the propofol group, which was not statistically significant. [2]
    • Miner JR et al 2015: Randomized, double-blind trial of propofol, 1:1 ketofol, vs 4:1 ketofol of 271 patients with a primary outcome of frequency of airway and respiratory adverse events leading to an intervention. The primary outcome occurred in 29% of the propofol group, 19% in the 1:1 ketofol group, vs 32% in the 4:1 ketofol group which was also not statistically significant. [3]

Author Conclusion: “Ketofol and propofol resulted in a similar incidence of adverse respiratory events requiring the intervention of the sedating physician. Although propofol resulted in more hypotension, the clinical relevance of this is questionable, and both agents are associated with high levels of patient satisfaction.”

Clinical Take Home Point: It appears that in adults requiring procedural sedation and analgesia, Ketofol has a similar incidence of adverse respiratory events requiring intervention when compared to propofol, but with the hypothetical addition of increased complexity of keeping track of multiple medications and syringes, that MIGHT LEAD to more medication errors (if you don’t play your cards right). At this time I would recommend folding your hand when it comes to ketofol.


  1. Ferguson I et al. Propofol or Ketofol for Procedural Sedation and Analgesia in Emergency Medicine – The POKER Study: A Randomized Double-Blind Clinical Trial. Ann Emerg Med 2016 [Epub Ahead of Print] PMID: 27460905
  2. Andolfatto G et al. Ketamine-Propofol Combination (Ketofol) Versus Propofol Alone for Emergency Department Procedural Sedation and Analgesia: A Randomized Double-Blind Trial. Ann Emerg Med 2012; 59 (6): 504 – 12. PMID: 22401952
  3. Miner JR et al. Randomized, Double-blinded, Clinical Trial of Propofol, 1:1 Propofol/Ketamine, and 4:1 Propofol/Ketamine for Deep Procedural Sedation in the Emergency Department. Ann Emerg Med 2015; 65: 479 – 488. PMID: 25441247

For More Thoughts on This Topic Checkout:

Post Peer Reviewed by: Scott Wieters (Twitter: @EMedCoach)

Cite this article as: Salim Rezaie, "The POKER Trial: Go All in on Ketofol?", REBEL EM blog, August 1, 2016. Available at:

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