Ketofol USE in the ED

1. Ketofol USE in the ED By Carmen Lau Pharmacy Year 4 December 27th, 2013

2. Procedural sedation and analgesia (PSA) Definition: A technique of administering sedatives w/ or w/o analgesics to induce a state that allows for unpleasant procedures, also referred to as conscious sedation Procedures • Setting fractures • Draining abscesses • Reducing dislocations • Endoscopy • Cardioversion • TEE and other imaging

3. Procedural sedation and analgesia (PSA) • The ideal drug • Easily titrated • Rapid onset • Brief duration of action • Provides adequate sedation and analgesia • Minimal respiratory and hemodynamic effects

4. Propofol

5. Propofol use in PSA Pro’s • Rapid onset, short duration of action, antiemetic effects Con’s • Use limited to dose-dependent respiratory depression and hypotension • Lack of analgesic effect: often co-administered with opioids but the combination increases likelihood of adverse airway events

6. Ketamine

7. Ketamine in PSA Pro’s • Preservation of airway reflexes • CV and respiratory stimulation • Analgesia Con’s • Longer recovery time • Recovery agitation and vomiting

8. Better together? Physically compatible when mixed in a single polypropylene syringe and stable at room temperature with exposure to light

9. The case 23yo 60kg F is brought to the ED with a dislocated left shoulder after a MVC. The physician decides to use ketofol for the procedure and asks you, the pharmacist, for help dosing the medication. How are you going to prepare this medication? Chem 7: Na 139, K 4.2, Cl 109, CO2 22, BUN 30, SCr 0.70, Glu 126 CBC: pending VS: HR 98, RR 22, Temp 37.6, BP 122/88

10. The 1st ketofol study(A prospective case series by Willman et al.)

11. Other ED ketofol case series

12. The case cont. 23yo 60kg F is brought to the ED with a dislocated left shoulder. The physician decides to use ketofol for the procedure. Chem 7: Na 139, K 4.2, Cl 109, CO2 22, BUN 30, SCr 0.70, Glu 126 CBC: pending VS: HR 98, RR 22, Temp 37.6, BP 122/88 You start to prepare ketofol at a 1:1 mixture of ketamine 10mg/ml and propofol 10mg/ml in a 10ml syringe. How much are you going to draw up, and how is the physician supposed to administer it?

13. Administration Approach 1 (Andolfatto et al.) • Initial dose= 0.375mg/kg of each ketamine and propofoladministered during 15-30sec • Every minute thereafter, the physician assesses the pt’s level of sedation and administers 0.188mg/kg of each drug if needed until sedation Approach 2 • Administer 1-3ml aliquots of 1:1 ketamine 10mg/ml and propofol 10mg/ml at the physician’s discretion

14. How to gauge sedation? • Physician assessment • Loss of lid reflexes, verbal response, tactile stimuli • Ramsay Sedation Scale <5 • Bispectral index (BIS) • Neurophysiological monitoring device that analyzes a pt’s electroencephalogram • Mostly used to assess deep anesthesia but is now studied in the ED

15. The case cont. 23yo 60kg F is brought to the ED with a dislocated left shoulder. The physician decides to use ketofol for the procedure. Chem 7: Na 139, K 4.2, Cl 109, CO2 22, BUN 30, SCr 0.70, Glu 126 CBC: pending VS: HR 98, RR 22, Temp 37.6, BP 122/88 • You mix 30mg (3ml) of ketamine and 30mg (3ml) of propofol in a syringe • The physician gives 3ml of the mixture (0.25mg/kg of each drug) initially, followed in 1min by the remainder 3ml • Adequate sedation was not reaches, so more ketofol was prepared and the physician gives another 3ml

16. The case cont. • A total of 9ml of the 1:1 mixture was administered • 9ml= 45mg of each drug • 45mg/60kg= 0.75mg/kg of each drug Remember that the median dose for the Willman et al. ketofol case series was 0.75mg/kg!!!

17. The case cont. The shoulder reduction was successful and the physician thanks you for your help. BP only dropped to 114/80 during the procedure. The patient will be discharged in about 1 hour after she recovers. The physician really likes ketofol, but wonders how it compares to other PSA agents. You tell him that…

18. Ketofol vs Propofol RCT

19. Ketofol vs Propofol Case Series • Phillips et al. 2010 • Prospective randomized case series of 28 patients >21yo • Propofol 0.5-1.5mg/kg vs. ketofol 0.75mg/kg • Measured procedural success, BIS score, adverse effects, recovery time, and VS • Results • Smaller % decline in SBP with ketofol (1.6% vs 12.5%) • Smaller difference between baseline and goal sedation BIS score with ketofol (18.78 vs 34.64) • Lower mean propofol dose with ketofol (92.5mg vs 177.27mg) • No respiratory depression in either group

20. Ketofol vs Propofol RCT

21. Ketofol vs Propofol RCT

22. Ketofol vs Propofol Recap • SBP • Less SBP % decrease with ketofol • Respiratory Depression • Similar if not fewer incidence of adverse respiratory events with ketofol • Sedation depth • Greater consistency based on Ramsay Scale and Colorado Behavioral Numerical Pain Scale with ketofol • Satisfaction score • Similar if not higher with ketofol • Mean propofol dose • Conflicting data, with most studies indicating less propofol required with ketofol

23. Ketofolvs Ketamine RCT

24. Ketofolvs Midazolam/Fentanyl RCT

25. Are the benefits clinically relevant? • Safe sedation can be achieved with just propofol • Induced hypotension is usually transient and self limiting • Using “extra” propofol doesn’t necessarily mean lengthened recovery time • No compelling evidence showing that ketofol greatly reduces respiratory depression compared to propofol • Ketamine works well alone if dissociative sedation is desired • Added complexity of administering 2 drugs and having to anticipate the side effects of both • It does not make sense pharmacokinetically to mix an ultrashort acting medication with another that isn’t

26. Conclusion • Ketofol provides adequate procedural sedation and analgesia • Ketofol is safe and effective: recovery times are short and adverse events are limited • Compared to other PSA agents, ketofol may have ↓ hypotension, ↓ respiratory depression, ↑ sedation quality, and ↑ patient satisfaction • It is still not certain whether ketofol offers clinically relevant benefits over either agent alone

27. Questions? Unrelated fun fact: Photofrin is a drug that requires lasers!!!

28. References Baker SN and Weant KA. Procedural Sedation and Analgesia in the Emergency Department. J Pharm Pract. 2011; 24(2): 189-195. Green SM, Andolfatto G, Krauss B. Ketofol for Procedural Sedation? Pro and Con. Ann Emerg Med. 2011; 57(5): 444-448. Willman EV, Andolfatto G. A Prospective Evaluation of “Ketofol” (Ketamine/Propofol Combination) for Procedural Sedation and Analgesia in the Emergency Department. Ann Emerg Med. 2007; 49(1): 23-30. Andolfatto G, Willman E. A Prospective Case Series of Single-syringe Ketamine-Propofol (Ketofol) for Emergency Department Procedural Sedation and Analgesia in Adults. AcadEmerg Med. 2011; 18: 237-245. Phillips W, Anderson A, Rosengreen M, et al. Propofol Versus Propofol/Ketamine for Brief Painful Procedures in the Emergency Department: Clinical and Bispectral Index Scale Comparison. J Pain Palliat Care Pharmacother. 2010; 24: 349-355. Andolfatto G, Abu-Laban RB, Zed PJ, et al. Ketamine-Propofol Combination (Ketofol) Versus Propofol Alone for Emergency Department Procedural Sedation and Analgesia: A Randomized Double-Blind Trial. 2012; 59: 504-512. Nejati, A. Moharari S, Ashraf H, et al. Ketamine/Propofol Versus Midazolam/Fentanyl for Procedural Sedation and Analgesia in the Emergency Department: A Randomized, Prospective, Double-blind Trial. AcadEmerg Med. 2011; 18: 800-806.