KetamineCan it tame the pain?

Casey Glass, MD Douglas Brtalik, MDChrist Post, MD

KetamineAn illustrated History

and Pharmacology

PCP

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

KetamineKetamine 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.

<1 minute

Once in the bloodstream ketamine redistributes to the CNS in ~45 seconds

4-5 minutes

Redistributes back to the body over 5 minutes

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

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

Ketamine has a remarkable ability to reduce the central

perception of pain, especially in chronic pain conditions that wind

up the CNS response.

The Literature

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

Motov 2015, PMID: 25817884

Motov 2015, PMID: 25817884

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

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

Sin 2015, PMID: 25716117

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

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

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

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

Ahern 2015, PMID: 25643741

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

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

Miller 2015, PMID: 25624076

Miller 2015, PMID: 25624076

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

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

Ketamine in Practice

When to use Ketamine

Opioid Tolerance/Abuse

TraumaNeuropathic

PainIntractable

Pain

Dosing for Acute PainIntravenous 0.15 - 0.3 mg/kg slow push(some recommend repeating dose over an hour after a load)

Intranasal: 0.7 - 1 mg/kg

Dose Adjustment for Size

Dose based on Ideal Body Weight, not Actual weight!

K Hole!

Give the loading dose slow Total dose based on IBW

ContraindicationsAllergy (only true absolute)

Severe hypertension

Chronic Liver Disease

Head Trauma?

Glaucoma?

Active Schizophrenia

Younger than 3 months

Adverse Reactions

Composite: Molotov 2015, Miller 2015, Ahern 2015Aggregate 58% of patients

Adverse ReactionsDisorientation/Mood: 36%

Dizziness/Sensory: 32%

Nausea/Vomiting: 14%

Composite: Molotov 2015, Miller 2015, Ahern 2015

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

For Debate

Is Ketamine analgesia a safe

and effective therapy?

For Debate

Is it appropriate to offer ketamine as a first line pain medication?

For Debate

What should patients be told when ketamine is offered for analgesia?

References

Available via Pubmed at http://1.usa.gov/1Y0Hqmr

Articles available for Wake residents and staff athttp://bit.ly/1mas1V2