Low Dose Discuss the history and pharmacology of ketamine - - PDF document

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Low Dose Ketamine...Everything?

Craig Smollin MD Associate Medical Director, California Poison Control Center, SF Division Assistant Professor of Emergency Medicine, UCSF

Objectives

• Discuss the history and pharmacology of ketamine
• Differentiate anesthetic from subanesthetic doses of

ketamine

• In what clinical scenarios might low dose ketamine be of

value?

• Pain management
• The agitated patient
• Airway management

Ketamine History

• 1958: PCP introduced into clinical anesthesia
• 1959: Cyclohexamine tried but found to be worse than PCP
• 1962: Ketamine synthesized by Stevens
• 1965: Ketamine trials in humans. Most promising of 200

different PCP derviatives

• 1970: Ketamine released for clinical use in U.S.

Mechanism of action

• Non-competative NMDA receptor antagonist
• NMDA receptor involved in sensory input at the spinal,

thalamic, limbic and cortical levels.

• Interferes with sensory input to higher centers of the CNS

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The role of NMDA receptors Definitions

• Anesthetic or dissociative
• Sub-dissociative

Sedation dosing

Route Dose Onset Time to peak effect Duration of action Intravenous 0.5-1.0 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 Can also be administered via oral and rectal routes, however with signficantly greater time to onset and duration of action.

Low-dose Ketamine

• Defined as the administration of 0.1 to 0.6 mg/kg IV

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Clinical Scenarios

• We will discuss the following clinical scenarios:
• A patient with a history of IVDU and high opiate tolerance

with a large deltoid abscess requiring incision and drainage.

• A child with a long bone fracture of the extremity.
• A 35 year old male with extreme agitation requiring

aeromedical transport to another facility

• A patient in respiratory distress on BIPAP

Clinical Scenario #1

• 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 area of erythema, swelling, and fluctulence over the left lateral

• deltoid. The patient complains of 10/10 pain and will barely

allow you to touch his arm. He is given a total of 4 mg of dilaudid without improvement in pain. How would you continue management of this patient given the need for an incision and drainage?

Opiate sparing effects

• Management of severe acute pain in emergency settings:

ketamine reduces morphine consumption. Am J. Emerg Med 2007; 25:385-90

• 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 to achieve

same pain scale scores (<30/100)

Opiate sparing effects

• Peri-operative ketamine for acute post-operative pain: a

quantitative and qualitative systematic review (Cochrane review) Acta Anaesthesiol Scand 2005;49:1405-142

• 27/37 trials found that peri-operative ketamine

reduced rescue analgesic requirements or pain intensity, or both.

• In the first 24 h after surgery, ketamine reduces

morphine requirements.

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Ketamine and agitation Ketamine and agitation

• Initial ketamine dosing range given was 0.5-1 mg/kg.
• If two doses required within first 60 min of initiation of sedation

infusion started at initial rate of 1-1.5 mg/kg per hour.

• The amount given was titrated to achieve a target sedation level that

was a calm, cooperative patient who could still respond to verbal commands.”