1. ABCs of Ketamine Safety Nicholas Filk, PharmD PGY-2 Emergency Medicine Pharmacy Resident Maimonides Medical Center Brooklyn, NY

2. Disclosures ■I have no relevant financial relationships to disclose at this time

3. Objectives ■Identify medication errors commonly associated with ketamine ■Describe methods of preventing ketamine medication errors in the Emergency Department

4. flickr.com

5. Ketamine: The Basics ■Mechanism of action –NMDA receptor antagonist RouteDosageOnset of actionDuration Intravenous0.15-2 mg/kg 30 seconds5-10 minutes Intramuscular2-5 mg/kg3-4 minutes15-25 minutes Intranasal0.5-1 mg/kg10 minutes~ 60 minutes Andolfatto G et al. Academic Emergency Medicine. 2013;20(10):1050-4. Green SM et al. Ann of Emer Med.57(5):449-61. doi: 10.1016/j.annemergmed.2010.11.030

6. Ketamine: The Basics ■Adverse events –Increased oral secretions –Laryngospasm –Hypertension –Emergence phenomena –Respiratory depression? Green SM et al. Ann of Emer Med.57(5):449-61. doi: 10.1016/j.annemergmed.2010.11.030 https://commons.wikimedia.org/wiki/File:Cloudland_waterfall_1.jpg

7. Ketamine use in the ED ■Induction agent for intubation ■Analgesic ■Bronchodilator ■Anxiolytic ■Procedural sedation ■∞ Ketamine cures all your ailments! http://loc.gov/pictures/resource/highsm.28650/

8. Concerns of Ketamine Use Multiple Routes Multiple Indications Multiple Dosages Multiple Concentrations High Alert Medication Dangerous Medication Errors

9. Wrong route: Intranasal vs Intramuscular 32 year old presents with acute agitation. Midazolam and haloperidol administered intramuscularly (IM) have failed. MD orders ketamine 4mg/kg IM x1 stat. Ketamine inadvertently administered intranasal (IN) versus IM. Did you say IN or IM? https://pixabay.com/en/syringe-healthcare-needle-medicine-417786/ www.dixieems.com

10. ISMP Recommendations INIntranasal or NAS https://www.ismp.org/tools/errorproneabbreviations.pdf Education, Education, and more Education!

11. Wrong dose A 6 year old is ordered ketamine for procedural sedation. The order is for 0.5mg/kg IV x1. Due to a math error 50mg/kg IV is given to the child. ED staff are alarmed that the child has not woken up after 30 minutes… http://www.ibiblio.org/wm/paint/auth/munch/munch.scream.jpg

12. Keep Calm or Sound the Alarm ■Green et al 1999 –Inadvertent ketamine overdoses in children –5-100 fold overdose (n=9) –Prolonged sedation (n=9) –Brief respiration depression (n=4) ■Intubation (n=2)…but precautionary Green SM, et al. Ann of Emerg Med. 1999;34(4 I):492-7

13. Proposed Solution ■Independent double verification –RN check RN, MD check RN, PharmD check RN ■Weight based dose sheets –Minimizes mathematic errors ■Technology –Electronic order entry

14. Wrong Concentration 35 year old male weighing 50kg presents with a severe asthma exacerbation. All primary and secondary agents have failed. Ketamine 1mg/kg IV x1 ordered. Patient has improved air movement but becomes unresponsive with respiratory depression requiring intubation.

15. What went wrong? ■Automated dispensing cabinet (ADC) –2 concentrations stocked –10mg/ml, 100mg/ml ■Dose administered –500mg vs. 50mg ordered

16. Proposed Solution ■Single IV concentration in the ED –10mg/ml ■Dispense IM and IN doses individually in syringe –50mg/ml or 100mg/ml ■Auxiliary labeling ■Technology –Prompts in ADCs

17. Ketofol: Tainted Milkshake ■Ketofol –Mixture of ketamine and propofol –Gaining popularity for procedural sedation –Ketamine reduces hypotension caused by propofol Thomas MC et al. AJHP. 2011;68:2248+. http://www.keepcalm-o-matic.co.uk/p/keep-calm-and-inject-ketofol-1/

18. Ketofol: Pitfalls ■Sterility issues –Lipid emulsion = bacterial petri dish ■Mixture ratios –MD preference versus standard ■Syringe contents –Propofol and ketofol undistinguishable ■Compatibility –Limited information https://www.ismp.org/Newsletters/acutecare/articles/A1Q12Action.asp https://commons.wikimedia.org/wiki/File:Ampoule_prefilled_JPN.jpg

19. Ketofol Solutions ■Promote sterility upon admixture ■Establish standard ratio for mixture ■Do not use the word “ketofol” ■Labeling

20. Key Takeaways Education of staff necessary for safe ketamine useAvoid stocking multiple concentrations in the EDUtilize electronic order entry whenever possibleErase ketofol from your dictionary!

21. What is a common medication error associated with ketamine? A.Wrong dose B.Wrong concentration C.Wrong route D.All of the above

22. What is/are possible method(s) of reducing concentration errors related to ketamine? A.Store one concentration in the ED B.Dispense IN and IM doses in patient specific syringes C.Place concentrated ketamine in separate ADC drawer D.A and B

23. References 1.Andolfatto G, Willman E, Joo D, Miller P, Wong WB, Koehn M, Dobson R, Angus Moadebi S. Intranasal ketamine for analgesia in the emergency department: A prospective observational series. Academic Emergency Medicine. 2013;20(10):1050-4. 2.Green SM, Roback MG, Kennedy RM, Krauss B. Clinical Practice Guideline for Emergency Department Ketamine Dissociative Sedation: 2011 Update. Annals of Emergency Medicine.57(5):449-61. doi: 10.1016/j.annemergmed.2010.11.030. 3.List of Error-Prone Abbreviations, Symbols, and Dose Designations: Institute For Safe Medication Practices 2015 [cited 2016 March 12]. Available from: https://www.ismp.org/tools/errorproneabbreviations.pdf. 4.Green SM, Clark R, Hostetler MA, Cohen M, Carlson D, Rothrock SG. Inadvertent ketamine overdose in children: Clinical manifestations and outcome. Annals of Emergency Medicine. 1999;34(4 I):492-7. 5.Thomas MC, Jennett-Reznek AM, Patanwala AE. Combination of ketamine and propofol versus either agent alone for procedural sedation in the emergency department. American Journal of Health-System Pharmacy. 2011;68:2248+. 6.ISMP Quarterly Action Agenda October - December 2011. ISMP Medication Safety Alert!: Acute Care [Internet]. 2012 March 12, 2016. Available from: https://www.ismp.org/Newsletters/acutecare/articles/A1Q12Action.asp.

24. https://imgflip.com/i/10y0et Questions?