Ketamine has been studied as an alternative to opioids for acute pain management in emergency department settings. Several randomized controlled trials found that low-dose ketamine administered intravenously or by infusion was as effective as morphine in reducing patient-reported pain scores over time intervals up to 2 hours. Ketamine appeared to provide pain relief more rapidly than morphine in some studies. Adverse effects were similar between ketamine and opioids but included disorientation, dizziness, and nausea. Emergence reactions occurred in a small percentage of patients receiving ketamine. While ketamine is a promising option, more research is still needed to establish its role as a first-line analgesic or compare its long-term risks and benefits to opioids.

1. Ketamine
Can it tame the pain?
Casey Glass, MD
Douglas Brtalik, MD
Christ Post, MD

2. Ketamine
An illustrated History
and Pharmacology

3. PCP

4. PCP accomplished general anesthesia levels of sedation but has
effects that are too long lasting

5. Ketamine
Ketamine was one of many derivatives of PCP and selected
for use due to more rapid resolution of effect. It was first
given to a human in clinical trials in 1964.

6. <1 minute
Once in the bloodstream ketamine redistributes
to the CNS in ~45 seconds

7. 4-5 minutes
Redistributes back to the body over 5 minutes

8. Ketamine is highly water soluble and not very lipophilic so has
small volume of distribution

9. Ketamine has a high affinity for the NMDA receptors in the CNS
and a lesser affinity for opioid receptors

10. Ketamine has a remarkable
ability to reduce the central
perception of pain, especially in
chronic pain conditions that wind
up the CNS response.

11. The Literature

12. Design: RCT
Single agent IV ketamine vs IV morphine
Outcome measures
• Self reported pain score at various intervals
• Need for rescue pain medication for
uncontrolled pain
Intravenous Subdissociative-Dose Ketamine Versus
Morphine for Analgesia in the Emergency Department:
A Randomized Controlled Trial
Sergey Motov, MD*; Bradley Rockoff, MD; Victor Cohen, PharmD; Illya Pushkar, MPH;
Antonios Likourezos, MA, MPH; Courtney McKay, PharmD; Emil Soleyman-Zomalan, MD;
Peter Homel, PhD; Victoria Terentiev, BA; Christian Fromm, MD
Motov 2015, PMID: 25817884

13. Motov 2015, PMID: 25817884

14. Motov 2015, PMID: 25817884

15. Study Conclusion
• Ketamine as effective as Morphine as single agent
• Higher proportion of patients who reported pain level
of zero without need of rescue opiate medication.
• Overall similar incidence of side effects but with
statistically significant increase in side effects
reported at time of injection with ketamine
Motov 2015, PMID: 25817884

16. The Use of Subdissociative-dose Ketamine for
Acute Pain in the Emergency Department
Billy Sin, PharmD, Theologia Ternas, PharmD, and Sergey M. Motov, MD
Sin 2015, PMID: 25716117
Design: Structured Review
4 studies from 1998 to 2008 totaling 428 patients
of which 260 are pediatric patients

17. Sin 2015, PMID: 25716117

18. Messenger et al, 2008; Galinski et al, 2007
Messenger et al
• Compared IV Fentanyl 1.5 mcg/kg vs .3 mg/kg Ketamine
• Primary outcome adverse events and pain levels
Galinski et al
• compared .2 mg/kg IV Ketamine over 10 min + .1mg/kg Morphine
over 10 min vs .1mg/kg morphine alone
Both showed no significant difference in patient pain or
adverse outcomes.
Sin 2015, PMID: 25716117

19. Gurnani et al, 2007
• Ketamine infusion vs IV opioid prn (standard of care)
• Patients receiving ketamine had significantly lower
pain scores
• Patients receiving ketamine consumed less morphine
• Interesting other observations noted
• No rescue pain meds needed with ketamine infusion group
(vs 90% in standard group)
• No side effects noted in this group
Sin 2015, PMID: 25716117

20. Conclusion
• Officially: “failed to provide enough evidence to
support or refute use of SDDK”
• Appears not inferior to IV narcotic alone
• Infusion ketamine as an option in ED??
Sin 2015, PMID: 25716117

21. Design: RCT
• Infusion ketamine rather than boluses for acute pain
• NOT comparing to IV opioids
• Allowed use of IV morphine in small doses q20 prn
• Followed pain scoring for 120 min
• Infusion for one hour then cut off for one hour
Brief Research Report:
Low-Dose Ketamine Infusion for Emergency
Department Patients with Severe Pain
Terence L. Ahern MD,* Andrew A. Herring MD, Steve Miller MD, and Bradley W. Frazee MD
Ahern 2015, PMID: 25643741

22. Ahern 2015, PMID: 25643741

23. Conclusion
• Pain scores at various intervals all decreased
• Rescue pain meds used in 58%
• Those that did not require other pain meds had much
better pain reduction than others
• Reports complete pain control at 10/60/120 mins were 75%;
100%; 83% vs those who got additional pain meds who
reported 36%; 53%; 61%
• Ketamine responders?
• Pt satisfaction 84%
Ahern 2015, PMID: 25643741

24. Design: RCT
• Superiority trial, ketamine compared to IV morphine
• Outcome measure was change in pt pain reported at
given time intervals
Low-dose ketamine vs morphine for acute pain in the
ED: a randomized controlled trial.
Miller JP, Schauer SG, Ganem VJ, Bebarta VS
Miller 2015, PMID: 25624076

25. Miller 2015, PMID: 25624076

26. Miller 2015, PMID: 25624076

27. Conclusion
• Similar pain management with ketamine and morphine
• No superiority
• DID note faster reported pain relief with ketamine
• Side effect reported similar
• Pt satisfaction similar
Miller 2015, PMID: 25624076

28. My take
• Ketamine well studied as adjunct to IV narcotics for acute
pain control
• Ketamine looks to work about as well as IV narcotics when
used in isolation
• Infusion ketamine
• No study found significant adverse events with use of
Ketamine

29. Ketamine in Practice

30. When to use Ketamine
Opioid
Tolerance/Abuse
Trauma
Neuropathic
Pain
Intractable
Pain

31. Dosing for Acute Pain
Intravenous
0.15 - 0.3 mg/kg
slow push
(some recommend
repeating dose over an
hour after a load)
Intranasal:
0.7 - 1 mg/kg

32. Dose Adjustment for Size
Dose based on Ideal Body Weight, not Actual weight!

33. K Hole!
Give the loading dose slow
Total dose based on IBW

34. Contraindications
Allergy (only true absolute)
Severe hypertension
Chronic Liver Disease
Head Trauma?
Glaucoma?
Active Schizophrenia
Younger than 3 months

35. Adverse Reactions
Composite: Molotov 2015, Miller 2015, Ahern 2015Aggregate 58% of patients

36. Adverse Reactions
Disorientation/Mood: 36%
Dizziness/Sensory: 32%
Nausea/Vomiting: 14%
Composite: Molotov 2015, Miller 2015, Ahern 2015

37. The Elephant in the room... Emergence Reactions!
• this likely represents partial dissociation
• Mild in ~6%, clinically significant in 1-2%
• Multifactorial related to dosage, patient
selection, age
• Not well studied in sub-dissociative
dosage
• Possibly related to improper dosing

39. For Debate
Is Ketamine
analgesia a safe
and effective
therapy?

40. For Debate
Is it appropriate to offer ketamine as
a first line pain medication?

41. For Debate
What should patients be told when
ketamine is offered for analgesia?

42. References
Available via Pubmed at
http://1.usa.gov/1Y0Hqmr
Articles available for Wake residents and staff at
http://bit.ly/1mas1V2