Current Concepts in Ketamine Therapy in the Emergency Department (Pharmacology CME and Pain Management CME)

Table of Contents

 

About This Issue

Ketamine has long-established uses in the emergency department, including analgesia, procedural sedation, and rapid sequence intubation; however, its atypical dose-response action must be taken into account for maximum effectiveness and to avoid distressing emergence reactions. As more ED uses for ketamine emerge, an understanding of the current state of evidence is crucial. In this issue, you will learn:

The differences in the pharmacokinetics and effects of an analgesic dose, a partially dissociative dose, and a dissociative dose.

Safe analgesic dosing and administration recommendations, to avoid and manage emergence reactions.

How to manage adverse effects of ketamine dosing in procedural sedation.

Rapid sequence intubation, delayed sequence intubation, and ketamine-only breathing intubation; when each is appropriate and how to dose, administer, and manage adverse effects.

When ketamine can be used to manage patient agitation and when alternative agents (eg, antipsychotics or benzodiazepines) should be used.

What the current evidence is on ED use of ketamine for asthma, status epilepticus, alcohol use disorder, and treatment-resistant depression.

1. About This Issue
2. Abstract
3. Case Presentations
4. Introduction
5. The Ketamine-Brain Continuum
   1. Analgesic Dose (0.1-0.3 mg/kg IV)6
   2. Recreational Dose (0.2-0.5 mg/kg IV)
   3. Partially Dissociated Dose (0.4-0.8 mg/kg IV)
   4. Dissociative Dose (≥1mg/kg IV)7
6. Analgesia
   1. Dosing and Administration for Analgesia
7. Procedural Sedation
   1. Dosing and Administration for Procedural Sedation
   2. Managing Adverse Effects
      1. Ketamine, Propofol, and Dexmedetomidine
8. Rapid Sequence Intubation
9. Alternatives to Rapid Sequence Intubation
   1. Delayed Sequence Intubation
   2. Ketamine-Only Breathing Intubation
10. Treatment of Agitation
    1. Dosing and Administration for Agitation
    2. Managing Adverse Effects and Monitoring Response
11. Future Directions: The Horizon of Ketamine Therapy in Emergency Medicine
    1. Asthma
    2. Status Epilepticus
    3. Alcohol Withdrawal Syndrome and Alcohol Use Disorder
    4. Treatment-Resistant Depression
12. 5 Things That Will Change Your Practice
13. Risk Management Pitfalls in Using Ketamine in the Emergency Department
14. Summary
15. Time- and Cost-Effective Strategies
16. Case Conclusions
17. Figures
18. References

Abstract

Ketamine has been in use since its development as a dissociative anesthetic in the 1960s, but it was largely confined to the operating theater or austere environments until used by emergency physicians to facilitate painful procedures in children. As the unique effects of ketamine across its dose-response curve were understood, new applications emerged. In low doses, ketamine has found an important role alongside or instead of opioids in the management of severe pain, and methods to slow its absorption allow higher, more effective doses while attenuating psychoperceptual effects. Ketamine’s unique anesthetic properties have inspired its use as an induction agent for intubation without a paralytic and for the rapid, safe control of dangerously agitated patients. Emerging uses for ketamine in acute care include treatment for status epilepticus and alcohol withdrawal syndrome; however, its most important rising indication may be as an emergency treatment of depression and suicidality.

Case Presentations

A 43-year-old man presents to the ED after a trip and fall onto his outstretched hand…

• The patient’s examination is notable for a dinner-fork deformity, and wrist radiograph shows a distal radius fracture with dorsal angulation.
• In order to reduce the fracture, procedural sedation with ketamine is performed. Though the usual dissociative dose of ketamine is ≥1 mg/kg IV, because you anticipated the procedure to be very brief, you chose a smaller dose of 40 mg.
• Shortly after administration, the patient begins screaming in terror and is obviously anguished by hallucinations and feelings of unreality. The clinical team is very concerned and looks to you for next steps…

A 22-year-old man presents after being thrown from his motorcycle; he was not wearing a helmet and has head injuries…

• Your primary survey demonstrates a low Glasgow Coma Scale score, failure to protect the airway, blood pressure of 77/40 mm Hg, and laxity on manual pelvic compression.
• Portable chest x-ray is unremarkable, but pelvic radiograph demonstrates an open-book pelvic fracture.
• You decide to intubate the patient for airway protection and presumptive need for operative management. Given the patient’s hypotension, you call for 100 mg of rocuronium and 75 mg ketamine for rapid sequence intubation. Your colleague voices concern that ketamine is contraindicated in brain-injured patients…

A 74-year-old woman presents with hematemesis…

• The patient has a history of metastatic pancreatic cancer and has palliative goals of care; she does not wish to have any life-extending procedures done.
• She is in severe cancer-related pain, but is on high doses of opioids at home and describes a recent ED presentation in which staff was unable to control her pain with usual doses of opioids.
• The patient and her husband request that no tests or treatments be done beyond making her comfortable. She knows she has reached the end of her life and asks whether there is anything you can give her besides opioids to take away her pain…

How would you manage these patients? Subscribe for evidence-based best practices and to discover the outcomes.

Risk Management Pitfalls in Using Ketamine in the Emergency Department

4. “We used propofol for RSI induction because ketamine is contraindicated in head trauma patients.” Ketamine does not meaningfully increase intracranial pressure and, unlike propofol, maintains blood pressure–a critical goal in neuro-resuscitation.

7. “We gave large doses of midazolam, but couldn’t calm the patient in time to prevent a bad outcome.” Dissociative-dose ketamine is the best agent to calm the uncontrollably violent patient, especially patients who are resistant to alternative treatments. Once a dissociative dose of ketamine is administered, the patient requires continuous resuscitation-level monitoring for the duration of dissociation.

8. “The patient had a Glasgow Coma Scale score of 3 after EMS gave a big dose of ketamine for agitation, so he required intubation.” Most patients treated for agitation with dissociative-dose ketamine will emerge from dissociation safely and not require intubation; however, preparation for intubation and vigilant monitoring of ventilation for the duration of dissociation is required.

Subscribe to access the complete Risk Management Pitfalls to guide your clinical decision making.

Figures

Subscribe for full access to Figures.

Key References

Following are the most informative references cited in this paper, as determined by the authors.

3. Gerber M. “Speakers Take a Close Look at Prehospital Ketamine Use at EMS World Expo.” 2023. Accessed April 10, 2024. (Website article)

4. Strayer R. “The Ketamine Brain Continuum.” 2013. Accessed April 10, 2024. (Website article)

9. American College of Emergency Physicians. Sub-dissociative dose ketamine for analgesia. 2018. Accessed April 10, 2024. (Policy statement)

13. * Clattenburg EJ, Hailozian C, Haro D, et al. Slow infusion of low-dose ketamine reduces bothersome side effects compared to intravenous push: a double-blind, double-dummy, randomized controlled trial. Acad Emerg Med. 2018;25(9):1048-1052. (Randomized controlled trial; 59 patients) DOI: 10.1111/acem.13428

23. * Dove D, Fassassi C, Davis A, et al. Comparison of nebulized ketamine at three different dosing regimens for treating painful conditions in the emergency department: a prospective, randomized, double-blind clinical trial. Ann Emerg Med. 2021;78(6):779-787. (Randomized controlled trial; 120 patients) DOI: 10.1016/j.annemergmed.2021.04.031

49. * Green SM, Roback MG, Krauss BS, et al. Unscheduled procedural sedation: a multidisciplinary consensus practice guideline. Ann Emerg Med. 2019;73(5):e51-e65. (Society guideline) DOI: 10.1016/j.annemergmed.2019.02.022

74. * Green SM, Andolfatto G, Krauss BS. Ketamine and intracranial pressure: no contraindication except hydrocephalus. Ann Emerg Med. 2015;65(1):52-54. (Editorial) DOI: 10.1016/j.annemergmed.2014.08.025

95. * Merelman AH, Perlmutter MC, Strayer RJ. Alternatives to rapid sequence intubation: contemporary airway management with ketamine. West J Emerg Med. 2019;20(3):466-471. (Review) DOI: 10.5811/westjem.2019.4.42753

100. Strayer R. “Ketamine-Only Breathing Intubation.” 2019. Accessed April 10, 2024. (Website article)

102. *Thiessen MEW, Godwin SA, Hatten BW, et al. Clinical Policy: critical issues in the evaluation and management of adult out-of-hospital or emergency department patients presenting with severe agitation: approved by the ACEP Board of Directors, October 6, 2023. Ann Emerg Med. 2024;83(1):e1-e30. (Clinical policy) DOI: 10.1016/j.annemergmed.2023.09.010

105. *Barbic D, Andolfatto G, Grunau B, et al. Rapid agitation control with ketamine in the emergency department: a blinded, randomized controlled trial. Ann Emerg Med. 2021;78(6):788-795. (Randomized controlled trial; 80 patients) DOI: 10.1016/j.annemergmed.2021.05.023

114. American College of Emergency Physicians. ACEP Task Force report on hyperactive delirium with severe agitation in emergency settings. 2021. Accessed April 10, 2024. (Task force report)

115. American Medical Association. Use of drugs to chemically restrain agitated individuals outside of hospital settings. Report 2 of the Council on Science and Public Health. 2021. Accessed April 10, 2024. (AMA report)

116. American Society of Anesthesiologists; American College of Emergency Physicians. ASA/ACEP joint statement on the safe use of ketamine in prehospital care. 2020. Accessed April 10, 2024. (Joint statement)

143. Megli D. “Ketamine Therapy for Mental Health a ‘Wild West’ for Doctors and Patients.” KFF Health News. 2024. Accessed April 10, 2024. (News article)

Subscribe to get the full list of 147 references and see how the authors distilled all of the evidence into a concise, clinically relevant, practical resource.

Keywords: ketamine, dissociative, procedural, analgesia, emergence, intubation, rapid, delayed, agitation, asthma, status epilepticus, depression, alcohol