Emergency Department use of Subdissociative-dose Ketamine for Treatment of Acute Pain

Transcription

1 Emergency Department use of Subdissociative-dose Ketamine for Treatment of Acute Pain LAUREN STANLEY, MD FACEP ASSISTANT MEDICAL DIRECTOR BOONE COUNTY EMERGENCY MEDICINE

2 Objectives By the end of this presentation, participants will be able to: Understand pharmacology of subdissociative-dose ketamine Identify target patient populations for use of subdissociative / analgesic-dose ketamine Understand the nuts and bolts of administering analgesic-dose ketamine (including dosing, monitoring recommendations, adverse reactions and their management) Evaluate and address staff and patient perception of treatment

3 Why are novel pain medications needed? Pain is most common presenting complaint to the Emergency Department

4 and we give A LOT of pain medications.

5 But we aren t always great at it! 1. Pain may be under-treated

6 Under treatment of pain Pain in the Emergency Department: Results of the Pain and Emergency Medicine Initiative (PEMI) Multicenter Study - Only 60% of patients received analgesics - lengthy delays (median, 90 minutes; range, 0 to 962 minutes) - 74% of patients were discharged in moderate to severe pain.

7 But we aren t always great at it! 1. Pain may be under-treated 2. or over-treated, leading to adverse effects (especially opioids)

8 But we aren t always great at it! 1. Pain may be under-treated 2. or over-treated, leading to adverse effects (especially opioids) Acute effects: respiratory depression, hypoxia, bradycardia, hypotension Long-term effects including opioid dependence/abuse, opioid-induced hyperalgesia (OIH)

9 Opioid-Induced Hyperalgesia = state of increased pain sensitization caused by exposure to opioids Related to abnormalities in glutamate system, NMDA receptor upgrading Allodynia Morphine can INCREASE the pain

10 Opioid epidemic Pain control

11 The History of Ketamine Synthesized in 1962 in attempt to find safer anesthetic alternative to PCP because of PCP s effects of hallucinations, mania, seizures First used on soldiers in WWII and Vietnam War

12 So, how does subdissociative-dose ketamine work? subdissociative mg/kg IV dissociative 1-2mg/kg IV PAIN CONTROL SEDATION

13 Mechanism of ketamine action Primarily acts as NMDA receptor antagonist - Belongs to family of receptors that mediate excitatory nerve transmission in the brain - Plays role in cellular mechanism for learning, memory

14 Mechanism of ketamine action Open NMDA channel allows Ca2+ ions to flow into the neuron

15 NMDA receptor antagonism Blocks flow of Ca2+ ions into neuron Blocked ability to process information sensory less, analgesia, amnesia, state of DISSOCIATION

16 Strong pain stimuli activate NMDA receptors and produce hyperexcitability of neurons Increased sensitization, wind up pain, pain memory Thus, Ketamine fights hyperalgesia and wind up pain Ketamine disrupts many downstream, longer-lasting cellular processes such as gene expression, protein regulation

17 Mechanism of ketamine action Also acts on opioid, GABA, cholinergic receptors sympathetic nervous system Antidepressant effects (serotonin activation) Increases endogenous inhibition of pain sensation Increases release of dopamine, norepinephrine; prevents uptake

18 What patient populations might benefit from subdissociative-dose ketamine?

19 (almost) ANYONE!!!

20 Target population 1: chronic opioid users Many have developed significant opioid tolerance and opioidinduced hyperalgesia, making traditionally used medications (such as fentanyl, morphine, hydromorphone) ineffective. Using high or frequent doses of opioids may also be unsafe because of progressive respiratory depression and cardiovascular effects (such as hypotension) despite lack of pain control

21 Target population 2: patients at risk for adverse effects of opioids The elderly Patients at risk for hypoventilation - For example, patients with acute intoxication who are already at risk for respiratory depression Hemodynamically unstable patients - Trauma, Burn

22 Target population 3: refractory pain despite typical meds

23 How does it compare to morphine? Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial [Ann Emerg Med. 2015;66: ] 90 patients enrolled, years old Musculoskeletal, flank, back, abdominal pain Morphine 0.1mg/kg or Ketamine 0.3mg/kg IV

24 Ketamine > morphine at 15 minutes, but no significant difference in pain scores at 30 minutes Baseline pain scores: 8.6 versus min: 4.1 versus 3.9 No significant difference in adverse effects - Ketamine patients reported increased minor adverse effects at 15 minutes 15min 30min 120min

25 Conclusion: Subdissociative intravenous ketamine administered at 0.3 mg/kg provides analgesic effectiveness and apparent safety comparable to that of intravenous morphine for shortterm treatment of acute pain in the ED.

26 Bottom line Ketamine is SAFE + EFFECTIVE

27 So, how do we do give ketamine for acute pain?

28 So, how do we do give ketamine for acute pain? Patient preparation: Cardiac and continuous SpO2 monitor Pre-ketamine vital signs (within 10 minutes of giving drug) Then repeated q15minutes until patient back at baseline mental status

29 DOSING mg/kg IV, with maximum bolus of 40mg average initial dose 10-20mg Onset of action: 30 seconds 1 min Peak effect: 1-5 minutes Duration of action: minutes

30 DOSING Or administer in 100mL 0.9% normal saline, infused over 10 minutes

31 DOSING Drip can be started after initial bolus: mg/kg/hr IV to prepare: ketamine 100 mg in 100 ml of 0.9% NS to make a 1mg/mL drip

32 Adverse effects of subdissociativedose ketamine aka what could go wrong?

33 Adverse effects of subdissociative-dose ketamine: Cardiovascular Arrhythmia (tachycardia most common) Hypertension

34 Adverse effects of subdissociative-dose ketamine: Psychiatric Agitation, delirium, confusion Hallucinations

35 Adverse effects of subdissociative-dose ketamine: Others Transient hypertonia and/or tonic clonic movements Transient laryngospasm Increased salivation and respiratory secretions Apnea, respiratory depression Nausea, vomiting Increase in ICP (Intracranial Pressure) or intraocular pressure Cardiovascular: bradycardia, hypotension

36 Adverse effects of subdissociative-dose ketamine Adverse effects are much less common than with DISSOCIATIVE-dose ketamine (ie for procedural sedation) Subdissociative Dissociative

37 Adverse effects of subdissociative dose ketamine: What do I do if these happen???

38

39 Adverse effects of subdissociative-dose ketamine: Management Supportive care measures!

40 Managing adverse effects of ketamine: supportive care measures For acute agitation, hallucinations: maintain calm, quiet environment, with dim lighting if possible use benzo s (lorazepam = Ativan; midazolam = Versed; etc)

41 Managing adverse effects of ketamine: supportive care measures For respiratory adverse reactions reposition head/airway apply supplemental oxygen as needed for hypoxia use suction for airway secretions bag-valve-mask assisted ventilation (or advanced airway techniques) as needed

42 Managing adverse effects of ketamine: supportive care measures For nausea/vomiting: ondansetron 4-8mg IV if not otherwise contraindicated

43 Managing adverse effects of ketamine: supportive care measures For hypotension: mL 0.9% NS IV bolus if not otherwise contraindicated

44 So, who SHOULDN T receive subdissociative-dose ketamine?

45 Absolute contraindications: 1. Allergy to ketamine 2. Age <3 months 3. Suspicion of acute primary psychotic condition such as schizophrenia

46 Relative Contraindications: Conditions in which elevated blood pressure would be hazardous - Acute angina - Acute heart failure

47 Relative Contraindications: Conditions in which elevated blood pressure would be hazardous - Acute angina - Acute heart failure Elevated intraocular pressure (such as acute glaucoma)

48 Relative Contraindications: Conditions in which elevated blood pressure would be hazardous - Acute angina - Acute heart failure Elevated intraocular pressure Patients with known or suspected upper airway obstruction

49 Relative Contraindications: Conditions in which elevated blood pressure would be hazardous - Acute angina - Acute heart failure Elevated intraocular pressure (such as acute glaucoma) Patients with known or suspected upper airway obstruction Cases in which elevated intracranial pressure is suspected (such as obstructive hydrocephalus) - CONTROVERSIAL

50 Relative Contraindications: Conditions in which elevated blood pressure would be hazardous - Acute angina - Acute heart failure Elevated intraocular pressure Patients with known or suspected upper airway obstruction Elevated ICP Acute thyrotoxicosis

51 Use caution with Mild-moderate hypertension, tachycardia Neurotic traits Acute alcohol intoxication

52 Patient and Staff Perception of Treatment

53 Patient Perception It works! Decreased time to pain control Adverse effects should be discussed prior to giving the medication

54 Staff Perception: Initial It s too much work! It makes patients crazy. Drug-seekers love it.

55 Staff Perception: After using it It s too much work! We do vital signs and put patients on monitors anyway! It makes patients crazy. Drug-seekers love it.

56 Staff Perception: Initial It s too much work! It makes patients crazy. Agitation/delirium are less common than with dissociative-dose ketamine Adverse effects (agitation) are easily managed with lorazepam Drug-seekers love it.

57 Staff Perception: Initial It s too much work! It makes patients crazy. Drug-seekers love it. Good! Their pain is treated effectively and they are ready to be discharged safely, more quickly than if traditional meds (opioids) were given.

58 Introducing a new Medication/Treatment Early adopters The Majority Late adopters

59 Staff Perception: Overall

60 SUMMARY Subdissociative-dose ketamine is a safe alternative to traditionally used pain medications in the Emergency Department, especially for: 1. Patients with chronic pain and on chronic opioids 2. Patients in whom opioids would be unsafe - Hypoventilation risk - Hypotensive 3. Patients with refractory pain (kidney stones, headaches, etc)

61 SUMMARY Ketamine primarily works as an NMDA receptor antagonist, but has activity at multiple other receptors as well

62 SUMMARY The main adverse effects include: - Tachycardia - Hypertension - Agitation - Delirium - Laryngospasm - Increased airway secretions

63 SUMMARY Due to cardiovascular and respiratory effects, patients should be on cardiac and SpO2 monitor throughout treatment Adverse effects can be managed by supportive care (especially benzo s!) Since implementation of protocol for subdissociative-dose ketamine at our hospital, patient and staff perception has been positive

64 Where to find our protocol Document share

65 Thank you! Questions?

66 CITATIONS 1. Todd, K. H., Ducharme, J., Choiniere, M., Crandall, C. S., Fosnocht, D. E., Homel, P., Tanabe, P., & PEMI Study Group. (2007). Pain in the emergency department: results of the pain and emergency medicine initiative (PEMI) multicenter study. The journal of pain, 8(6), Smith, R. J., Rhodes, K., Paciotti, B., Kelly, S., Perrone, J., & Meisel, Z. F. (2015). Patient perspectives of acute pain management in the era of the opioid epidemic. Annals of emergency medicine, 66(3), Cordell, William H., et al. "The high prevalence of pain in emergency medical care." The American journal of emergency medicine 20.3 (2002): Martin, J. S., and R. Spirig. "Pain prevalence and patient preferences concerning pain management in the emergency department." Pflege 19.6 (2006): Safe use of opioids in hospitals. Sentinel Event Alert 2012: Sleigh, Jamie, et al. "Ketamine More mechanisms of action than just NMDA blockade." Trends in Anaesthesia and Critical Care 4.2 (2014): Hocking, Graham, and Michael J. Cousins. "Ketamine in chronic pain management: an evidence-based review." Anesthesia & Analgesia 97.6 (2003):

67 CITATIONS 8. Motov, S., Rockoff, B., Cohen, V., Pushkar, I., Likourezos, A., McKay, C., & Fromm, C. (2015). Intravenous subdissociative-dose ketamine versus morphine for analgesia in the emergency department: a randomized controlled trial. Annals of emergency medicine, 66(3), Miller, J. P., Schauer, S. G., Ganem, V. J., & Bebarta, V. S. (2015). Low-dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial. The American journal of emergency medicine, 33(3), Richards, J. R., & Rockford, R. E. (2013). Low-dose ketamine analgesia: patient and physician experience in the ED. The American journal of emergency medicine, 31(2), Sin, B., Ternas, T., & Motov, S. M. (2015). The use of subdissociative dose ketamine for acute pain in the emergency department. Academic Emergency Medicine, 22(3), (review article) 12. Lee M, Silverman SM, et al. A comprehensive rview of opioid-induced hyperalgesia. Pain Physician, 14(2):145.

68 CITATIONS 13. Ahern, T. L., Herring, A. A., Anderson, E. S., Madia, V. A., Fahimi, J., & Frazee, B. W. (2015). The first 500: initial experience with widespread use of low-dose ketamine for acute pain management in the ED. The American journal of emergency medicine, 33(2), Ahern, T. L., Herring, A. A., Stone, M. B., & Frazee, B. W. (2013). Effective analgesia with lowdose ketamine and reduced dose hydromorphone in ED patients with severe pain. The American journal of emergency medicine, 31(5), Zeiler, F. A., Teitelbaum, J., West, M., & Gillman, L. M. (2014). The ketamine effect on ICP in traumatic brain injury. Neurocritical care, 21(1),

69 Subdissociative Ketamine for Analgesia in Adults: Proposed protocol for use Indication: acute pain (traumatic or non-traumatic) in patients >16 years of age Mechanism of action: primarily acts as NMDA receptor antagonist. - Also acts on multiple other receptors including opioid, GABA, cholinergic; sympathetic nervous system - Increases endogenous inhibition of pain sensation - Prevents hyperalgesia and pain wind up Target patient populations: - Patients with severe pain refractory to other analgesics (including opioids such as morphine, hydromorphone, fentanyl; anti-inflammatory medications, such as toradol; acetaminophen). May be used as adjunct to these other medications, or as solo agent. - Patients with chronic pain, especially those who are opioid-tolerant o Many patients on chronic opioids have developed significant opioid tolerance and opioid-induced hyperalgesia, making traditionally used medications (such as fentanyl morphine, hydromorphone) ineffective. o Using high or frequent doses of opioids may also be unsafe because of progressive respiratory depression and cardiovascular effects (such as hypotension) despite lack of pain control - Patients at risk for compromised airway patency, hypoventilation, or hemodynamic instability if given opioid medications o Ketamine causes minimal central respiratory depression, so is safer for use in patients at risk for hypoventilation o Ketamine s cardiovascular effects are usually stimulatory (ie, hypertension instead of hypotension), so safer for use in patients at risk for hypotension Contraindications: - Absolute: o Previous allergy to ketamine o Age < 3 months o suspicion of acute psychotic condition including schizophrenia - Relative: o Cases in which elevated intracranial pressure is suspected (such as hydrocephalus) o Elevated intraocular pressure (such as acute glaucoma) o condition in which elevated blood pressure would be hazardous (such as acute angina, acute heart failure) o Use with caution in patients with acute alcohol intoxication o Acute thyrotoxicosis o Patients with known or suspected upper airway obstruction

70 Monitoring requirements for administration - Continuous Cardiac and oxygen saturation monitoring established before administration - Baseline vital signs (heart rate, blood pressure, respiratory rate, oxygen saturation) documented within 10 minutes prior to medication administration; then repeat vital signs every 15 minutes after medication administration, until patient returns to pretreatment level of awareness and verbalization - Baseline and post-medication pain scores as per nursing protocol - Notify physician/provider if: o heart rate <60 or >110 o systolic blood pressure <90 or >180 o respiratory rate <10 o development of hallucinations or acute agitation or combativeness Dose: mg/kg IV, with maximum bolus of 40mg (average dose 10-20mg) - Alternatively, 2mg/kg IM - When given IV: administer over at least 1 minute; alternatively, may administer as IVP with 100mL 0.9% normal saline, infused over 10 minutes - Following initial bolus, may be used as continuous infusion: 10-20mg/hr IV (to prepare: ketamine 100 mg in 100 ml of 0.9% NS to make a 1mg/mL drip) Possible adverse reactions: - Arrhythmia (tachycardia most common) - Hypertension (hypotension less common) - Recovery agitation, delirium, confusion - Hallucinations - Transient hypertonia and/or tonic clonic movements - Transient laryngospasm - Apnea, respiratory depression - Nausea, vomiting - Increased salivation and respiratory secretions - Note: adverse reactions occur more commonly when medication is used at dissociative doses Reversal agent: none Management of adverse reactions: supportive care - For respiratory adverse reactions: reposition head/airway, apply supplemental oxygen as needed for hypoxia, use suction for airway secretions, use bag-valve-mask assisted ventilation (or advanced airway techniques) as needed - For acute agitation, hallucinations: maintain calm, quiet environment, with dim lighting if possible; see adjunctive medications below

71 - For nausea/vomiting: ondansetron 4-8mg IVP if not otherwise contraindicated - For hypotension: mL 0.9% NS IV bolus if not otherwise contraindicated Adjunctive medications: - benzodiazepines for agitation, hallucinations o lorazepam mg/kg IV (maximum dose 2mg IV) o midazolam mg/kg (average dose 0.5 4mg) o consider co-administration of benzodiazepine with ketamine o or, benzodiazepine can be administered in a PRN fashion (PRN agitation, hallucinations) - consider giving hydromorphone 0.5-1mg IV for persistent pain Selected articles with relevant data Ahern TL, Herring AA, Stone MB, et al. Effective analgesia with low-dose ketamine and reduced dose hydromorphone in ED patients with severe pain, Amer J Emerg Med, 2013;31(5): Ahern TL, Herring AA, Anderson ES, et al, The first 500: initial experience with widespread use of low-dose ketamine for acute pain management in the ED, Amer J Emerg Med, 2015;33(2): Sleigh J, Harvey M, Voss L, et al, Ketamine: More mechanisms of action than just NMDA blockade, Trends in Anesthesia and Critical Care 2014;4:76-81 Green SM, Roback MG, Kennedy RM, et al, "Clinical Practice Guideline for Emergency Department Ketamine Dissociative Sedation: 2011 Update," Ann Emerg Med, 2011;57(5): Hocking G and Cousins MJ, "Ketamine in Chronic Pain Management: An Evidence-Based Review," Anesth Analg, 2003, 97(6): Kurdi MS, Theerth KA, Deva RS, Ketamine: Current applications in anesthesia, pain, and critical care, Anesth Essays Res. 2014;8(3): Motov S, Rockoff B, Cohen V, et al, Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med Mar 26 (EPub ahead of print) Shankar R, Wilson JA, Colvin L, Non-opioid-based adjuvant analgesia in perioperative care, Cont Edu Anaesth Crit Care & Pain, 2013;13(5): (May 2015)