2/16/2014 How do you use ketamine in your practice of emergency - PDF document

2/16/2014 How do you use ketamine in your practice of emergency medicine? Low Dose Ketamine...Everything? • Procedural sedation in children? Adults? • Induction agent for RSI? • Treatment of pain Craig Smollin MD Associate Medical Director, • Control of the agitated patient California Poison Control Center, SF Division Assistant Professor of Emergency Medicine, UCSF Is there more than anecdotal evidence to Objectives the use of low dose ketamine? • 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 1

2/16/2014 The history of ketamine starts with PCP The history of ketamine starts with PCP • 1958: Phencyclidine (PCP) introduced into Phencyclidine Ketamine PCP clinical anesthesia • 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

2/16/2014 Mechanism of action NMDA Receptors • Neurotransmitter glutamate • Glutamate released with noxious peripheral stimuli • Complex pharmacology • Activation of NMDA receptors associated: • Non-competative NMDA receptor antagonist • Hyperalgesia • Neuropathic pain • Reduced opioid sensitivity. Dissociative Dosing What is low-dose Ketamine? • “Poorly” defined as • Time to peak Duration of Route Dose Onset 0.1 - 0.6 mg/kg IV effect action • 0.5 - 1.0 mg/kg IM (reference below) • Intravenous 1.0 mg/kg < 1 min 3-5 min 5-10 min 0.5 mg/kg IN • 70 kg male doses between 7 to 40 mg IV Intramuscular 2-4 mg/kg 2-5 min 20 min 30 min Nasal 5 mg/kg 10 min 20 min 1 hour 3

2/16/2014 Clinical Scenario #1 Why even consider? • A 13 year-old female with no sig • PMH presents to the ED with a May provide effective analgesia left arm deformity after a • Can be given by a number of different routes skateboard accident. Exam is • significant for an obvious Airway responses are protected deformity above the right elbow. • The patient is neurovascular Minimal cardiovascular effects intact distal to the injury site. • Rapid onset, short duration of action, titratable She is crying and reports 9/10 pain. Ketamine for acute pain - Evidence 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 • • 40 adults with acute musculoskeletal trauma Prospective cohort study in prehospital setting • • SQ ketamine 0.1 mg/kg/hr vs IV Morphine 0.1 mg/kg 27 patients • • Pain relief better with ketamine (VAS) Rx groups: Morphine vs. Morphine + ketamine • • Patients in ketamine group had less drowsiness and Pain scores lower in morphine/ketamine group were easier to mobilize (traction/splinting) • • Blood pressure was high in morphine/ketamine group Nausea and vomiting in morphine group high • No pts in ketamine groups required supplemental Conclusion: Morphine + LDK provides adequate analgesia pain relief in patients with bone fractures 4

2/16/2014 Ketamine for acute pain - Evidence 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 • 65 trauma patient with acute pain Conclusion: Subcutaneous ketamine safe and • IV morphine injection of 0.1 mg/kg, followed by 3 mg effective analgesia in acute musculoskeletal trauma 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? Ketamine for acute pain - Evidence • Case series of 40 patients with mod to severe pain • IN ketamine 0.5 mg/kg initial bolus Conclusion: Low dose ketamine reduced morphine • requirements but with higher neuropsych side effects IN ketamine 0.25 mg/kg single repeat dose prn • Objective pain measurements (VAS) 5

2/16/2014 Intranasal ketamine for pain? Intranasal ketamine for pain? Conclusion: IN ketamine provides rapid, well-tolerated and clinically significant analgesia in ED patients Intranasal ketamine? Intranasal ketamine for pain? • 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.... 6

2/16/2014 Clinical Scenario #1 Clinical Scenario #1 • A 13 year-old female with no sig PMH Several small studies suggest presents to the ED with a left arm efficacy in this setting deformity after a skateboard accident. • Intranasal route is compelling Exam is significant for an obvious deformity above the right elbow. The • May obviate need for close patient is neurovascular intact distal respiratory monitoring to the injury site. She is crying and • reports 9/10 pain. More studies are needed Ketamine for acute pain - Evidence Clinical Scenario #2 • A 35 year old male with h/o IV heroin abuse presents with a left deltoid • 2 year retrospective review of pts receiving ketamine in the abscess. Exam sig for a 10 x 7 cm left lateral deltoid abscess. He ED complains of 10/10 pain and will • LDK defined as < 0.6 mg/Kg for pain control barely allow you to touch his arm. He • 35 cases identified screams out in pain when the nurse attempts to place an IV. Home meds • Most common use was abscess include methadone 120 mg daily. He is given a total of 4 mg of dilaudid • Chronic pain medication use described in 80% of cases without improvement in pain. How • Low dose ketamine improved pain in 54% of cases would you continue to manage of this patient? 7

2/16/2014 Ketamine for acute pain - Evidence Evidence in opiate tolerant patients? Conclusion: ED physicians used low dose ketamine • Randomized, double blind study design primarily in patient with high opiate tolerance • 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. Evidence in opiate tolerant patients? • 31 yo male with SCC • Fentanyl PCA • Oxycodone Conclusion: Preemptive bolus dose of ketamine has • opiate sparing effects in opioid abusers undergoing Ketorolac • moderate sedation Methadone • “Doctor it’s a 12!!” Venlafexine • Gabapentin • After 30 days of admission, placed on ketamine infusion with marked improvement in pain. 8

2/16/2014 Evidence in opiate tolerant patients? Clinical Scenario #2 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 14/17 cases showed improvement in pain continue to manage of this patient? Clinical Scenario #3 Clinical Scenario #2 • • A 35 year-old male with a Several small studies suggest a particular benefit of LDK in this patient history of alcohol abuse population presents brought in by medics • after he was found down on Likely reduces opiate consumption the sidewalk with a large • Needs to be studies in a controlled hematoma to his parietal scalp. fashion in the emergency department Upon arrival in the emergency setting. department he is agitated, spitting and attempting to hit multiple staff members. 9

2/16/2014 Ketamine for agitation? Ketamine for agitation? Here using dissociative dosing 5 mg/kg IM Ketamine and agitation Ketamine and agitation • 4/19 patients with tachycardia and hypertension • Case series of psychiatric patients undergoing aeromedical • 1/19 vomiting but no intervention required transport. • • No cases in which psychiatric symptoms were deemed Initial ketamine dosing range given was 0.5-1 mg/kg. • If two doses required infusion started at initial rate of 1-1.5 to have worsened. mg/kg per hour. • Authors conclude: ketamine sedation valid and safe • Amount given titrated to achieve a “calm, cooperative strategy for managing the agitation of psychiatric patient who could still respond to verbal commands.” patients.aeromedical transport 10