Pharmacology 101: The Pros and Cons of Ketamine

Pharmacology 101 is an online column designed to keep EMS providers informed on formularies, dosages, effects, applications, and current research related to medications administered in the prehospital setting. If you have a medication-related question you’d like the author to address, contact editor@emsworld.com.

Ah, ketamine. Perhaps the black sheep of a medic’s tool kit, it’s often regarded as a capricious medication, effective in many cases but perhaps just as likely to create a new set of problems. The FDA’s approved indications are quite narrow and permit its use in anesthesia settings and to supplement low-potency agents such as nitrous oxide.¹ However, it is used off-label for analgesia, agitation, and even depression.^2–4 In animals it’s used as a horse tranquilizer, and while its trade names are Ketalar and Ketaset, as a substance of abuse it enjoys other street names, such as special K, vitamin K, Kit Kat, keller, blind squid, cat Valium, purple, and super acid.⁵

While ketamine’s inclusion in prehospital formularies seems to have increased over the years, it does not appear to have yet reached universal acceptance, even with recent calls for its use. One recent article’s title simply states “It’s Time for EMS to Administer Ketamine Analgesia.”⁶ Publications document its use in prehospital and emergency department settings with titles such as “Let’s ‘Take ’Em Down’ With a Ketamine Blow Dart” and “Use of Ketamine for Prehospital Pain Control on the Battlefield.”^7,8

So what is ketamine, and why is there such an interest in its use in prehospital and emergency settings?

The Ideal Sedating Agent?

Here’s some basic pharmacology: it’s a dissociative anesthetic that acts on N-methyl-D-aspartate receptors as well as various opioid receptors, also interfering with nitric oxide synthesis, producing both sedative and analgesic effects.^9–11

Now, since we’re talking pharmacology, let’s pretend we’re in the lab and someone has asked us to design the ideal sedating agent for an agitated patient. New Jersey emergency physician Scott Mankowitz and colleagues describe it best:¹⁰ You’d want a fast onset and a moderate duration of effect—too fast, and you’ll have to keep redosing it; too long, and you’ll be waiting around for it to wear off. You’ll want it to be hemodynamically stable and probably avoid impairing respiratory drive. While we’re at it, add a reversal agent and a wide therapeutic range so we don’t have to do precise dosing calculations.

Does ketamine fit this bill? It has excellent pharmacokinetics: a rapid onset and short duration of action. It’s generally felt to be neutral in terms of respiratory effects (although it can occasionally cause respiratory depression) and may cause mild to moderate increases in heart rate, blood pressure, and cardiac output that are well tolerated in healthy patients.^7,9 In the ED it’s been used for a variety of indications, including procedural sedations, analgesia, rapid sequence intubation, and even as a bronchodilator for treatment of asthma.¹⁰ Unable to get IV access? Good news: Ketamine can be delivered orally, intravenously, intramuscularly, intranasally, or intraosseously.^9,10

Notable adverse side effects include hypersalivation and airway secretions, laryngospasm, hypertension, tachycardia, respiratory depression, and emergency syndromes (acute psychosis as the drug wears off). There’s some controversy due to conflicting data regarding the potential for harm in patients with elevated intracranial pressure.^7,9–11 Unfortunately there’s no reversal agent—if the patient receives a dissociative dose, you’ll have to wait for it to wear off, and the patient will traverse the continuum of effects ranging from dissociation (higher doses) to partial dissociation, then the recreational effects, and lastly subdissociative analgesia (lower doses). The good news is that ketamine’s duration of effect is fairly short.

The bottom line: In the prehospital setting agitated patients may present a danger to themselves and others. Ketamine has been noted as an agent that may provide rapid sedation for the control of agitated or violent patients. Other authors add, “Although not devoid of risks, [ketamine] may represent the best option when there is truly an imminent threat to patient and caregiver safety.”⁷ Mankowitz et al. note ketamine has a strong association with intubation, far more common when used in the prehospital setting for ground transport than in the ED or air medical transport.¹⁰

Prehospital ketamine studies continue to emerge,^9,12–14 and with the growing interest in its use in these settings, prehospital caregivers should carefully consider the pros and cons of adding ketamine to their formulary by familiarizing themselves with the most up-to-date literature.

References

1. JHP Pharmaceuticals LLC. KETALAR—ketamine hydrochloride injection package insert, 2012.

2. Andolfatto G, Innes K, Dick W, et al. Prehospital Analgesia With Intranasal Ketamine (PAIN-K): A Randomized Double-Blind Trial in Adults. Ann Emerg Med, 2019; 74(2): 241–50.

3. Burnett AM, Salzman JG, Griffith KR, Kroeger B, Frascone RJ. The emergency department experience with prehospital ketamine: A case series of 13 patients. Prehosp Emerg Care, 2012; 16(4): 553–9.

4. Wilkinson ST, Sanacora G. Considerations on the off-label use of ketamine as a treatment formood disorders. JAMA, 2017; 318(9): 793–4.

5. Stewart CE. Ketamine as a street drug. Emerg Med Serv, 2001; 30(11).

6. Cousins R, Anderson D, Dehnisch F, Brown A, McKay S, Glassman ES. It’s Time for EMS to Administer Ketamine Analgesia. Prehosp Emerg Care, 2017; 21(3): 408–10.

7. Green SM, Andolfatto G. Let’s “Take ’Em Down” with a Ketamine Blow Dart. Ann Emerg Med, 2016; 67(5): 588–90.

8. De Rocquigny G, Dubecq C, Martinez T, et al. Use of ketamine for prehospital pain control on the battlefield: a systematic review. J Trauma Acute Care Surg, 2019.

9. Keseg D, Cortez E, Rund D, Caterino J. The use of prehospital ketamine for control of agitation in a metropolitan firefighter-based EMS system. Prehosp Emerg Care, 2015; 19(1): 110–15.

10. Mankowitz SL, Regenberg P, Kaldan J, Cole JB. Ketamine for Rapid Sedation of Agitated Patients in the Prehospital and Emergency Department Settings: A Systematic Review and Proportional Meta-Analysis. J Emerg Med, 2018; 55(5): 670–81.

11. Walls R, Hockberger R, Gausche-Hill M, eds. Rosen’s Emergency Medicine: Concepts and Clinical Practice: Volume 1&2, 9th ed. Philadelphia: Elsevier Health Sciences, 2017.

12. Cole JB, Driver BE, Klein LR, Moore JC, Nystrom PC, Ho JD. In reply: Ketamine is an important therapy for prehospital agitation—Its exact role and side effect profile are still undefined. Am J Emerg Med, 2018; 36(3): 502–3.

13. Cole JB, Moore JC, Nystrom PC, et al. A prospective study of ketamine versus haloperidol for severe prehospital agitation. Clin Toxicol, 2016; 54(7): 556–62.

14. Cole JB, Klein LR, Nystrom PC, et al. A prospective study of ketamine as primary therapy for prehospital profound agitation. Am J Emerg Med, 2018; 36(5): 789–96.

Daniel Hu, PharmD, BCCCP, has Doctor of Pharmacy degree and is a critical care and emergency medicine pharmacist. He is a frequent speaker at conferences and has many publications in peer-reviewed journals.