Low Dose Ketamine

2/16/2014
How do you use ketamine in your practice of

emergency medicine?
Low Dose Ketamine...Everything?
Craig Smollin MD
Associate Medical Director,
California Poison Control Center, SF Division
Assistant Professor of Emergency Medicine, UCSF
Is there more than anecdotal evidence to

the use of low dose ketamine?
Procedural sedation in children? Adults?

Induction agent for RSI?
Treatment of pain
Control of the agitated patient
Objectives
History and pharmacology of ketamine

Anesthetic vs. sub-anesthetic doses of ketamine
Clinical scenarios and evidence
taken from Saturday Morning Breakfast

http://www.smbc-comics.com
2/16/2014
The history of ketamine starts with PCP
1958: Phencyclidine (PCP) introduced into

clinical anesthesia
The history of ketamine starts with PCP
Phencyclidine
Ketamine
PCP
Anesthetic effects attributed to NMDA

receptor antagonism
Hallucinations, confusion, and delirium led

to its discontinued use in humans
Ketamine History
Ketamine
1962: Ketamine synthesized by Stevens
1965: Ketamine trials in humans. Most
promising of 200 different PCP derivatives
1970: Ketamine released for clinical use in
U.S.
2/16/2014
Mechanism of action
NMDA Receptors
Complex pharmacology
Neurotransmitter glutamate
Glutamate released with noxious peripheral stimuli
Activation of NMDA receptors associated:
Non-competative NMDA receptor antagonist
Dissociative Dosing
Hyperalgesia
Neuropathic pain
Reduced opioid sensitivity.
What is low-dose Ketamine?
Route
Dose
Onset
Time to peak
effect
Duration of
action
Intravenous
1.0 mg/kg
< 1 min
3-5 min
5-10 min
Intramuscular
2-4 mg/kg
2-5 min
20 min
30 min
Nasal
5 mg/kg
10 min
20 min
1 hour
Poorly defined as
0.1 - 0.6 mg/kg IV

0.5 - 1.0 mg/kg IM (reference below)
0.5 mg/kg IN
70 kg male doses between 7 to 40 mg IV
2/16/2014
Clinical Scenario #1
Why even consider?
May provide effective analgesia

Can be given by a number of different routes
Airway responses are protected
Minimal cardiovascular effects
Rapid onset, short duration of action, titratable
A 13 year-old female with no sig

PMH presents to the ED with a
left arm deformity after a
skateboard accident. Exam is
significant for an obvious
deformity above the right elbow.
The patient is neurovascular
intact distal to the injury site.
She is crying and reports 9/10
pain.
Ketamine for acute pain - Evidence

Gurnani A. et al. Analgesia for acute musculoskeletal
trauma: low-dose subcutaneous infusion of ketamine.
Anaesth Intensive Care 1996 Feb; 24(1): 32-6
Prospective cohort study in prehospital setting

27 patients
Rx groups: Morphine vs. Morphine + ketamine
Pain scores lower in morphine/ketamine group
Blood pressure was high in morphine/ketamine group
Conclusion: Morphine + LDK provides adequate

pain relief in patients with bone fractures
40 adults with acute musculoskeletal trauma

SQ ketamine 0.1 mg/kg/hr vs IV Morphine 0.1 mg/kg
Pain relief better with ketamine (VAS)
Patients in ketamine group had less drowsiness and
were easier to mobilize (traction/splinting)
Nausea and vomiting in morphine group high
No pts in ketamine groups required supplemental
analgesia
2/16/2014

Gurnani A. et al. Analgesia for acute musculoskeletal
trauma: low-dose subcutaneous infusion of ketamine.
Anaesth Intensive Care 1996 Feb; 24(1): 32-6
Conclusion: Subcutaneous ketamine safe and

effective analgesia in acute musculoskeletal trauma
65 trauma patient with acute pain

IV morphine injection of 0.1 mg/kg, followed by 3 mg
every 5 hours
Placebo (saline) or ketamine 0.2 mg/kg over 10
minutes
Ketamine group required much less morphine
Ketamine group higher incidence of neuropsych side
effects
Intranasal ketamine for pain?
Conclusion: Low dose ketamine reduced morphine

requirements but with higher neuropsych side effects
Case series of 40 patients with

mod to severe pain
IN ketamine 0.5 mg/kg initial bolus
IN ketamine 0.25 mg/kg single
repeat dose prn
Objective pain measurements
(VAS)
2/16/2014
Conclusion: IN ketamine provides rapid, well-tolerated

and clinically significant analgesia in ED patients
Intranasal ketamine?
Prospective, randomized controlled equivalence

trial
Children with isolated musculoskeletal limb injury
Rx groups: IN ketamine (1 mg/kg) vs IN fentanyl
(1.5 ug/kg)
Outcome = median change in pain scores
Awaiting results....
2/16/2014
A 13 year-old female with no sig PMH

presents to the ED with a left arm
deformity after a skateboard accident.
Exam is significant for an obvious
deformity above the right elbow. The
patient is neurovascular intact distal
to the injury site. She is crying and
reports 9/10 pain.
Several small studies suggest

efficacy in this setting
Intranasal route is compelling

May obviate need for close
respiratory monitoring
More studies are needed

A 35 year old male with h/o IV heroin

abuse presents with a left deltoid
abscess. Exam sig for a 10 x 7 cm
left lateral deltoid abscess. He
complains of 10/10 pain and will
barely allow you to touch his arm. He
screams out in pain when the nurse
attempts to place an IV. Home meds
include methadone 120 mg daily. He
is given a total of 4 mg of dilaudid
without improvement in pain. How
would you continue to manage of this
patient?
2 year retrospective review of pts receiving ketamine in the

ED
LDK defined as < 0.6 mg/Kg for pain control
35 cases identified
Most common use was abscess
Chronic pain medication use described in 80% of cases
Low dose ketamine improved pain in 54% of cases
2/16/2014
Conclusion: ED physicians used low dose ketamine

primarily in patient with high opiate tolerance
Evidence in opiate tolerant patients?
Randomized, double blind study design

Rx groups: Ketamine 0.1 mg/kg vs Placebo
Both groups received intermittent doses of remifentanyl
during the procedure
Ketamine group required lower doses of opiates and had
improved pain scores.
Conclusion: Preemptive bolus dose of ketamine has

opiate sparing effects in opioid abusers undergoing
moderate sedation
31 yo male with SCC
Fentanyl PCA
Oxycodone
Ketorolac
Methadone
Venlafexine
Doctor its a 12!!
Gabapentin
After 30 days of admission, placed on ketamine infusion with

marked improvement in pain.
2/16/2014
A 35 year old male with h/o IV heroin
abuse presents with a left deltoid abscess.
Exam sig for a 10 x 7 cm left lateral deltoid
abscess. He complains of 10/10 pain and
will barely allow you to touch his arm. He
screams out in pain when the nurse
attempts to place an IV. Home meds
include methadone 120 mg daily. He is
given a total of 4 mg of dilaudid without
improvement in pain. How would you
continue to manage of this patient?
14/17 cases showed improvement in pain
Several small studies suggest a
particular benefit of LDK in this patient
population
Likely reduces opiate consumption

Needs to be studies in a controlled
fashion in the emergency department
setting.
A 35 year-old male with a

history of alcohol abuse
presents brought in by medics
after he was found down on
the sidewalk with a large
hematoma to his parietal scalp.
Upon arrival in the emergency
department he is agitated,
spitting and attempting to hit
multiple staff members.
2/16/2014
Ketamine for agitation?
Ketamine for agitation?
Here using dissociative dosing

5 mg/kg IM
Ketamine and agitation
Case series of psychiatric patients undergoing aeromedical

transport.
Initial ketamine dosing range given was 0.5-1 mg/kg.
If two doses required infusion started at initial rate of 1-1.5
mg/kg per hour.
Amount given titrated to achieve a calm, cooperative
patient who could still respond to verbal commands.
Ketamine and agitation
4/19 patients with tachycardia and hypertension

1/19 vomiting but no intervention required
No cases in which psychiatric symptoms were deemed
to have worsened.
Authors conclude: ketamine sedation valid and safe
strategy for managing the agitation of psychiatric
patients.aeromedical transport
10
2/16/2014
What about ketamine and potential head

injury?
Evidence that ketamine elevates ICP is

weak
No evidence that ketamine causes harm

in TBI
Ketamines hemodynamic stability may
be of benefit in TBI
Intriguing data from case

reports and case series
Higher doses may be required
Concern of administration in
psychiatric patients may be
overblown
Need more ED based studies
A 35 year-old male with a

history of alcohol abuse
presents brought in by medics
after he was found down on
the sidewalk with a large
hematoma to his parietal scalp.
Upon arrival in the emergency
department he is agitated,
spitting and attempting to hit
multiple staff members.
A 16 year-old female with h/o

severe asthma and prior
intubations presents with acute
onset of SOB and wheezing.
Exam is significant for hypoxia
with O2 sat 90%, tachypnea, and
wheezes with diminished air
movement bilaterally. She is
initially treated with albuterol,
atrovent, and steroids without
significant improvement.
11
2/16/2014
Low dose ketamine in the asthmatic
Low dose ketamine in the asthmatic
Randomized, double blind, placebo controlled study

design
Conclusion: Low dose ketamine had no

incremental benefit compared with placebo
68 patients enrolled
Rx groups: ketamine (0.2 mg/kg + infusion) vs placebo
Outcome: validated asthma score
Results: No difference between the two groups
A 16 year-old female with h/o

severe asthma and prior
intubations presents with acute
onset of SOB and wheezing.
Exam is significant for hypoxia
with O2 sat 90%, tachypnea, and
wheezes with diminished air
movement bilaterally. She is
initially treated with albuterol,
atrovent, and steroids without
significant improvement.
No real indication for low dose

ketamine here
Higher doses of ketamine may be
beneficial
Furthers studies needed
12
2/16/2014
The bottom line...
Thank You
Multiple studies demonstrate LDK effective in the treatment

of acute pain.
LDK appears reduces opiate requirements
Questions?
LDK may be particularly effective in patient with high opioid

tolerance
Unclear utility of low dose ketamine in the agitated patient
LDK does not appear to improve outcomes in nonintubated
asthmatics
References
Johansson P, et. al The effect of combined treatment with morphine sulphate and low-dose
ketamine in a prehospital setting, Scandinavian Journal of Trauma, Resuscitation and
Emergency Medicine
Gurnani A. et al. Analgesia for acute musculoskeletal trauma: low-dose subcutaneous
infusion of ketamine. Anaesth Intensive Care 1996 Feb; 24(1): 32-6
Galinski M, et al. Management of severe acute pain in emergency settings: ketamine reduces
morphine consumption. Am J Emerg Med. 2007;25:385-390.
Andolfatto, G et. al, Intranasal Ketamine for Analgesia in the Emergency Department: A
Prospective Observation Series. Academic Emergency Medicine. Oct 2013;20(10) 1050-4
Lester L, Braude DA, Niles C, Crandall CS, et al. Low-dose ketamine for analgesia in the ED:
a retrospective case series. Am J Emerg Med. 2010;28:820-876
Gharaei B, et. al. Opioid-Sparing Effect of Preemptive Bolus Low-Dose Ketamine for
Moderate Sedation in Opioid Abusers Undergoing Extracorporeal Shock Wave Lithotripsy: A
Randomized Clinical Trial. Anesthesia and Analgesia Jan 2013; 116(1) 75-80
Uprety D, et. al Ketamine infusion for sickle cell pain crisis refractory to opioids: a case report
and review of literature
Roberts J., et al. Intramuscular ketamine for the Rapid Tranquilization of the Uncontrollable,
Violent, and Dangerous Adult Patient. J Trauma. 2001;51:1008-1010
Cong M, et. al. Ketamine sedation for patients with acute agitation and psychiatric illness
requiring aeromedical retrieval Emerg Med J 2012 29:335-337
Allen J, et. al. The Efficacy of Ketamine in Pediatric Emergency Department Patients Who
Present With Acute Severe Asthma. J of Emer Med 2011, 41(5)492-494
13

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2/16/2014

How do you use ketamine in your practice of

Low Dose Ketamine...Everything?

Is there more than anecdotal evidence to

Procedural sedation in children? Adults?

History and pharmacology of ketamine

taken from Saturday Morning Breakfast

The history of ketamine starts with PCP

1958: Phencyclidine (PCP) introduced into

The history of ketamine starts with PCP

Anesthetic effects attributed to NMDA

Hallucinations, confusion, and delirium led

Non-competative NMDA receptor antagonist

What is low-dose Ketamine?

0.1 - 0.6 mg/kg IV

70 kg male doses between 7 to 40 mg IV

Why even consider?

May provide effective analgesia

A 13 year-old female with no sig

Ketamine for acute pain - Evidence

Prospective cohort study in prehospital setting

Conclusion: Morphine + LDK provides adequate

40 adults with acute musculoskeletal trauma

Ketamine for acute pain - Evidence

Ketamine for acute pain - Evidence

Conclusion: Subcutaneous ketamine safe and

Ketamine for acute pain - Evidence

65 trauma patient with acute pain

Intranasal ketamine for pain?

Conclusion: Low dose ketamine reduced morphine

Case series of 40 patients with

Intranasal ketamine for pain?

Intranasal ketamine for pain?

Conclusion: IN ketamine provides rapid, well-tolerated

Intranasal ketamine for pain?

Prospective, randomized controlled equivalence

A 13 year-old female with no sig PMH

Several small studies suggest

Intranasal route is compelling

More studies are needed

Ketamine for acute pain - Evidence

A 35 year old male with h/o IV heroin

2 year retrospective review of pts receiving ketamine in the

Ketamine for acute pain - Evidence

Conclusion: ED physicians used low dose ketamine

Evidence in opiate tolerant patients?

Randomized, double blind study design

Evidence in opiate tolerant patients?

Conclusion: Preemptive bolus dose of ketamine has

31 yo male with SCC

Doctor its a 12!!

After 30 days of admission, placed on ketamine infusion with

Evidence in opiate tolerant patients?

14/17 cases showed improvement in pain

Likely reduces opiate consumption

A 35 year-old male with a

Ketamine for agitation?

Ketamine for agitation?