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Three Part Question

In [adult patients requiring procedural sedation in the emergency department] does the use of [ketamine-propofol (ketofol)] compared to [propofol] decrease the [occurrence of adverse effects]?

Clinical Scenario

A 65-year-old male with history of atrial fibrillation on apixaban presents to the emergency department with recurrent atrial fibrillation with a rapid ventricular rate. His vitals are stable and physical exam reveals irregularly irregular heart rate. He states medications to covert atrial fibrillation are usually ineffective and he requests cardioversion. However, he expresses concern about the side effects he experienced during his last procedural sedation with propofol.

Search Strategy

Medline 1966-05/24 using PubMed, Cochrane Library (2024), and Embase
[(ketofol OR ketamine-propofol) AND (propofol) AND (procedural sedation) AND (emergency)]. LIMIT to Adults, English language.

Search Outcome

28 studies identified; one systematic review and two clinical studies were identified as both relevant and of sufficient quality for inclusion.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Andolfatto G, et al March 2012 British Columbia, Canada	284 patients requiring procedural sedation were randomly assigned to receive either propofol or ketofol.	RCT	Adverse respiratory events	Similar in both groups	Different clinicians may have different intervention thresholds, and use of the same weight-based dosing schedule for procedures of varied painfulness may have affected the incidence of adverse events.
			Procedural agitation	3.5% ketofol versus 11% propofol
			Hypotension	0% ketofol versus 0.7% propofol
			Muscular rigidity	0% ketofol versus 1.0% propofol
Jalili, M et al. March 2016 Tehran, Iran	18 RCTs met inclusion criteria comparing administration of ketofol with propofol for procedural sedation and analgesia.	Meta-analysis	Respiratory complications	Relative risk 0.31 favoring ketofol (p=0.001)	Pooled results of several studies with different designs, procedure types, and settings.
			Hypotension	Relative risk 0.11 favoring ketofol (p=0.04)
			Bradycardia	Relative risk 0.47 favoring ketofol (p=0.008)
			Psychomimetic complications	Relative risk 1.95 (p=0.15)
			Muscle rigidity	Relative risk 0.52 favoring ketofol (p=0.56))
Ferguson I, et al November 2016 Australia	573 patients who required deep procedural sedation to facilitate performance of a painful procedure in the ED were given a weight-based dose of either propofol or ketofol.	RCT	Frequency of airway and respiratory adverse events	27% propofol versus 21% ketofol (not significant)	Convenience sample, selection bias, and subjectivity in outcome measure.
			Hypotension	8% propofol versus 1% ketofol (not significant)
			Patient satistaction	Both agents are associated with high levels of patient satisfaction

Comment(s)

Ketofol is associated with less respiratory depression, hypotension, and bradycardia when compared with propofol alone. The clinical significance of this is minimal, however, with respiratory events and hypotension requiring no more intervention than a fluid bolus or transient bag-valve mask ventilation, overall with similar outcomes and patient satisfaction.

Clinical Bottom Line

Ketofol decreases the incidence of respiratory events and hypotension during procedural sedation. However, this likely has minimal long-term clinical impact on patient outcomes.

References

1. Andolfatto G, Abu-Laban RB, Zed PJ, Staniforth SM, Stackhouse S, Moadebi S, Willman E. Ketamine-propofol combination (ketofol) versus propofol alone for emergency department procedural sedation and analgesia: a randomized double-blind trial. Ann Emerg Med 2012 Jun;59(6):504-12
2. Jalili M, Bahreini M, Doosti-Irani A, Masoomi R, Arbab M, Mirfazaelian H. Ketamine-propofol combination (ketofol) vs propofol for procedural sedation and analgesia: systematic review and meta-analysis. Am J Emerg Med 2016 Mar;34(3):558-69.
3. Ferguson I, Bell A, Treston G, New L, Ding M, Holdgate A. Propofol or Ketofol for Procedural Sedation and Analgesia in Emergency Medicine-The POKER Study: A Randomized Double-Blind Clinical Trial. Ann Emerg Med 2016 Nov;68(5):574-582.