Ketamine-propofol (Ketofol) for Procedural Sedation
Date First Published:
May 28, 2024
Last Updated:
July 10, 2024
Report by:
Nathan DeBruine MD, Thomas Peterson MD, EM senior resident, EM faculty (Corewell Health - Michigan State University Emergency Medicine Residency Program, Grand Rapids, MI)
Search checked by:
Jeffrey S. Jones MD, Corewell Health - Michigan State University Emergency Medicine Residency Program, Grand Rapids, MI
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
Search Details:
[(ketofol OR ketamine-propofol) AND (propofol) AND (procedural sedation) AND (emergency)]. LIMIT to Adults, English language.
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):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Ketamine-propofol combination (ketofol) versus propofol alone for emergency department procedural sedation and analgesia: a randomized double-blind trial. Andolfatto G, Abu-Laban RB, Zed PJ, Staniforth SM, Stackhouse S, Moadebi S, Willman E. Mar-12 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 | ||||
| Ketamine-propofol combination (ketofol) vs propofol for procedural sedation and analgesia: systematic review and meta-analysis. Jalili M, Bahreini M, Doosti-Irani A, Masoomi R, Arbab M, Mirfazaelian H. Mar-16 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)) | ||||
| Propofol or Ketofol for Procedural Sedation and Analgesia in Emergency Medicine-The POKER Study: A Randomized Double-Blind Clinical Trial. Ferguson I, Bell A, Treston G, New L, Ding M, Holdgate A. Nov-16 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 |
Author Commentary:
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.
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:
- 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.
- 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.
- 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.