Paul Stromberg, MD

Carilion Clinic

VACEP

February 11, 2017

KETAMINE IN THE ED

FINANCIAL DISCLOSURES

• NONE

OUTLINE

• History and background

• Pharmacology/Mechanism of action

• Excited delirium

• Analgesia

• Depression

• Wrap-up

• PCP: Park Davis 1956

• 1961 Ketamine

synthesized

• 1/10th the potency

• 1964: First anesthetic

use in humans

• Ketalar approval 1970

KETAMINE

PHARMACOLOGY

• Arylcycloalkamine

• Racemic mixture of R and S isomers

• S (+) ketamine: higher anesthetic potency, decreased

emergence reactions

• R (-) ketamine: more potent antidepressant effects

• CYP 3A4: norketamine (30% the activity)

• Highly fat soluble

Li and Vlisides 2016

Gao et al, 2016

EXCITED DELIRIUM

• Altered mental status

• Often aggressive, “superhuman”

• Hyperthermia, tachycardia, hypertensive

• Danger to self and others

• High mortality, especially when forcibly restrained

• Numerous case reports of Ketamine for transporting

agitated patients

PREHOSPITAL IM KETAMINE

• Jan 2011 – May 2014

• 52 patients, effective in 50 patients

• Time to effective sedation and control approximately 2 mins

• Half the patients got midazolam per protocol

• Three cases of respiratory depression, 2 intubations (all got midazolam)

PREHOSPITAL AND RETRIEVAL

• Retrospective chart review 2013

• 163 encounters, 160 patients (2 repeat patients)

• 153 encounters analyzed in study

• 68% for analgesia, 25% for agitation

• 17% required intubation (most in ED after arrival)

• Mix of IV and IM (nearly 80% for agitation IM)

KETAMINE FOR ANALGESIA

• Prehospital

• In the ED

• Orthopedic injuries, all pain, migraines

• IM, IV, continuous infusions, IN

KETAMINE AND OPIOID SPARING

EFFECTS

• Primary mechanism of action is NMDA

antagonism

• Also binds to spinal mu and delta opioid

receptors

• May block opioid hyperalgesia

LOW DOSE KETAMINE

• Primary outcome: pain relief

• Followed for 2 hours post-ketamine (30, 60, 120)

• Secondary outcome: pain relief at each scoring

• Adverse effects collected

• Greater pain relief in ketamine groups, more sustained at higher dose, dizziness frequent complaint (50%)

Ahern, et al. 2015

KETAMINE INFUSION FOR SEVERE PAIN

• Prospective open-label study June 2013-Feb 2014

• 38 patients

• 15 mg bolus of ketamine, 20 mg/h infusion for 1h

• Offered additional analgesia at 20, 40, 60 min

• Pain assessed every 5-15 min for 120 min

• Primary outcome: change in pain

• Secondary outcomes: adverse effects, acceptability to patients

KETAMINE INFUSION

• Minimal sedation noted, no hypoxia

• Transient hypertension and tachycardia

• 85% would use ketamine for pain again

IN KETAMINE

• 1.0 mg/kg IN ketamine; 0.1 mg/kg IV morphine;

0.15 mg/kg IM morphine

• Pain and VS assess every 5 min for 1 hour

• Primary outcome: pain reduction of 15 mm on

VAS

• Adverse effect information collected

IN KETAMINE FOR PAIN RELIEF

• No difference in maximal pain relief or time to

maximal pain relief between groups

• Higher proportion of dizziness and difficulty

concentrating in ketamine group

• No difference in patient satisfaction between

groups

KETAMINE FOR DEPRESSION

• Emerging evidence for effectiveness in

management of severe depression

• Impact on suicidal ideation

• Glucose metabolism alteration in mood centers

• May be related to ketamine’s ability to alter

glutamate in the brain

Han, et al. 2016

KETAMINE FOR DEPRESSION

• Meta-analysis of 9 RCTs

• 368 total patients, 0.5 mg/kg IV ketamine

• Primary end-point of 50% reduction of symptoms

• Screened at 24 hrs, 72 hrs, and 7 days post-infusion

• Significantly more responders at all time points in the ketamine groups compared to placebo

IN KETAMINE, NOT JUST FOR PAIN

IN KETAMINE FOR DEPRESSION

• 18 patient cross-over study

• April 2012-June 2013

• 21-65, failed at least 1 anti-depressant in current episode

• 50 mg of IN ketamine or IN saline, switched 1 week later

• Primary outcome 50% reduction in depression symptoms

IN KETAMINE FOR DEPRESSION

• Significant difference in depressive symptoms as

early as 4 hours post insufflation

• 44% of patients met primary endpoint at 24

hours

• No significant difference at 3 days or 7 days

• No significant difference in adverse effects

compared to placebo

CONCLUSIONS

• Ketamine provides rapid sedation of agitated

patients

• Ketamine control associated with higher rate of

intubation

• May be useful adjunct in pain control

armamentarium

• Stay tuned for role in acute treatment of depression

THANK YOU

REFERENCES• GJ Hollis, et al. Emergency Medicine Australasia (2017) 29, 89-95

• JB Cole, et al. Clinical Toxicology, 2016. Vol. 54, No. 7, 556-562.

• Lovisk, et al. Scandinavian Journal of Trauma, Resuscitation, and Emergency Medicine (2015). 23:94.

• LN Petz, et al. Military Medicine, 180, 3:14, 2015.

• E Wiel, et al. Prehospital Emergency Care. January/March 2015. Volume 19/Number 1

• Lee EN, Lee JH. (2016). PLoS ONE 11(10).

• TL Ahern, et al. Pain Medicine 2015; 16: 1402-1409.

• FL Beaudoin, et al. Academic Emergency Medicine 2014. Vol. 21, No. 11.

• Lauristen, et al. The Journal of Headache and Pain (2016) 17:106.

• L Li, PE Vlisides. Frontiers in Human Neuroscience. November 2016. Vol. 10. Article 612.

• Han, et al. Neuropsychiatric Disease and Treatment 2016:12 2859-2867.

• Shimonovich, et al. BMC Emergency Medicine (2016) 16:43.

• Lapidus, et al. Biol Psychiatry. 2014 December 15; 76(12): 970-976.

• Gao, et al. Acta Pharmacologia Sinica (2016) 37: 865-872.

• D. Reicher. Air Medical Journal 35 (2016) 84-85.

• KA Scheppke, et al. Western Journal of Emergency Medicine. Volume XV, No 7: November, 2014.

• Ch Schultz. West J Emerg Med. 2104; 15(7): 742-743.