Get down that K-Hole! Ketamine for Control of the Agitated Adult Emergency Department Patient

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http://gomerblog.com/2015/12/angry-patient/

http://gomerblog.com/2015/12/angry-patient/

Background

Agitation in the Emergency Department is a reality and there are ramifications for the staff and of course the patient.  There are multiple causes for agitation ranging from psychiatric illness to drug intoxication and it can be difficult to know the etiology early in the ED course.  The optimal way to control agitation is to verbally de-escalate or have compliance with oral medications. Unfortunately, this may not be feasible and rapid sedation may be indicated.  The goal for rapid sedation or tranquilization should be appropriate, safe sedation with the first dose of medication utilized.

 

Other Agents for agitation

Historically agents such as benzodiazepines and antipsychotics have been used.  Dosing is empiric and often required re-dosing (Wilson 2012)

  • Benzodiazepines IV or IM (lorazepam, diazepam, midazolam)
    • May require very large doses
  • Antipsychotics PO, IV, IM (haloperidol, olanzapine, ziprasidone)
    • Longer onset of action
    • May require multiple doses
    • Potential for more adverse events
    • Concern for respiratory adverse events with combination (Powney 2012)
    • Ketamine has been used more recently both pre-hospital and in the emergency department

Ketamine

  • Background

    • It is a non-competitive NMDA receptor antagonist
    • Used for procedural sedation in the emergency department (pediatric and adult patients)
    • Sub-dissociative doses can be used for pain
    • Provides rapid amnesia and analgesia
    • Used as an induction agent for rapid sequence intubation
    • There are older case reports of use for agitation (Roberts 2001)
    • Goal is the rapid, first-dose control of the agitated patient
    • Dosing 
      • 1-2mg/kg IV, 4-5mg/kg IM
    • Onset
      • 1-2 min IV, 5-10 min IM
    • Duration
      • Variable, 20 min-120 min
    • Not titrated, there is a threshold for dissociation

  • Clinical effects

    • Dissociative, “trance-like” state (affectionately called the "K-hole")
    • Intact airway response
    • Intact hemodynamics

  • Adverse events

    • Tachycardia
    • Hypoxia
    • Hypertension
    • Laryngospasm
    • Emergence reaction
    • Nausea and vomiting
    • Increased intracranial and intraocular pressure

  • Contraindications

    • Psychosis (Lahti 1995)
      • Volunteer study, 9 patients
      • Sub-anesthetic doses
      • Short term symptoms similar to underlying psychiatric disorder
      • None required treatment
      • It is important to point out that the data for the contraindication in psychosis was a very small volunteer study using sub-dissociative dosing, not the dissociative dosing used for control of agitation. As far as I am aware, none of the studies below report worsening behavior or psychosis with ketamine use

Pre-Hospital Studies

  • Use of Ketamine for Agitated Patients in the Prehospital Setting: A systematic Review of the Literature (Schaeffer, Kralik, Strout)
    • Five studies reported 43 adverse events in 41 patients (23%)
      • Endotracheal intubation (N = 17, 9%). Most of them were in the Emergency Department
      • Hypertension or tachycardia within 72 hours (N = 10, 6%)
      • Hypoxia or respiratory depression (N = 7, 4%)
      • Emergence reaction (N = 3, 2%)
      • Laryngospasm (N = 2, 1%)
    • All studies reported improvement in agitation or increased sedation following ketamine

Take home: It seems like too many intubations but most were intubated in the ED. It was effective, and there were no behavioral adverse events.

  • A Ketamine Protocol and Intubation Rates for Psychiatric Air Medical Retrieval (Le Cong, Humble)
    •  Retrospective review of intubation rates before and after implementation of a ketamine sedation protocol for transfer of agitated patients
    • Overall intubation rates went from 3.5% to 2.3%
    • Lower rates with their docs v. contracted docs
    • Lots of questions with this study….
      • No discussion of what the “protocol” is
      • No discussion of protocol violations or compliance with use
      • No discussion of what other meds were used (or their doses)
      • Was there bias in that the docs that used ketamine like ketamine?
      • Really needs to be better studied
 

Emergency Department Studies

  • Ketamine as Rescue Treatment for Difficult-to-Sedate Severe Acute Behavioral Disturbance in the ED (Isbister, Calver, Downes, Page)
    • Used as a rescue agent, so patients received droperidol or another agent such as a benzodiazepine
    • 53 received ketamine, 4 excluded no prior meds
    • 3/4 sedated, 2 at 10 minutes and 1 at 20 minutes
    • 49 patients met inclusion
    • 45 (90%) achieved sedation within 20 min of KT
    • Five patients (10%) were not sedated within 120 minutes
    • Doses administered in these patients were 100, 150, 150, 200, and 400 mg
    • Median time to sedation post-KT was 20 min (60 min from protocol initiation)
    • Adverse events in 3 patients after ketamine (6%)
      • 2 vomiting
      • 1 transient hypoxia treated with oxygen only
  • A Novel Agent for Management of Agitated Delerium, A Case Series of Ketamine Utilization in the Pediatric ED (Kowalski, Kopec, Lavelle, Osterhoudt)
    • Case series of 5 patients (age 14-18) requiring rapid tranquilization
    • Undifferentiated diagnosis
      • Substance abuse and psychiatric diagnosis
      • Some received prior agents without success
      • Variable doses (lower than recommended doses)
      • Hemodynamically stable
      • No adverse events reported
  • Ketamine Use for Agitation in the ED (Hopper, Vilke, Castillo, Campillo, Davie, Wilson)
    •  Review of a historical cohort of patients receiving ketamine
    • 32 cases over 7 years
    • 17 IM and 15 IV
    • 18 cases received medication prior to ketamine
    • 20 cases required further medication, most commonly more ketamine after initial sedation
    • No clinically relevant change in BP or HR
    • No hypoxia in any patients
    • Treatment failures were associated with lower doses
    • Drug intoxication required high doses

 

Conclusion

  • Although there haven’t been large numbers of studies, use has been increasing both in the prehospital and ED settings. Its characteristics such as rapid onset, preservation of respiratory drive, and minimal hemodynamic effects make it potentially desirable as a first-dose control agent. Although pre- hospital data shows unexpected rates of intubation it is unclear the reason for all the intubations (perhaps from ED physician discomfort when they come in sedated?). We will need to continue following data.
  • The ED data is encouraging with very low rates of intubation and adverse events with well  described successful sedation.
  • It is interesting that some of the failures seem to be described with lower doses but not all data support this.
  • It is important to remember the the goal of ketamine is to get control of the dangerously agitated patient, not treat the underlying cause of agitation. This will need to be addressed with further treatment as indicated once they are able to be safely evaluated.
 

Written Tammi H. Schaeffer, DO, FACEP, FACMT
Edited and Posted by Jeffrey A. Holmes, MD

REFERENCES

1.  Vilke GM, Wilson MP. Agitation: what every emergency physician should know. Emerg Med Rep 2009;30:233–44.

2.  Wilson MP, Pepper D, Currier GW, Holloman GH, Feifel D. The psychopharmacology of agitation: consensus statement of the Amer- ican Association for Emergency Psychiatry Project BETA Psycho- pharmacology Workgroup. West J Emerg Med 2012;13:26–34.

3.  Bergman SA. Ketamine: review of its pharmacology and its use in pediatric anesthesia. Anesth Prog 1999;46:10–20.

4.  Richmond JS, Berlin JS, Fishkind A, et al. Verbal de-escalation of the agitated patient: consensus statement of the American Association for Emergency Psychiatry Project BETA De-escalation Work- group. West J Emerg Med 2012;13:17–25.

5.  Roberts JR, Geeting GK. Intramuscular ketamine for the rapid tranquilization of the uncontrollable, violent, and dangerous adult patient. J Trauma 2001;51:1008–10.

6.  Powney MJ, Adams CE, Jones H. Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation). Cochrane Database Syst Rev. 2012;(11):CD009377.

7.  Hopper AB, Vilke GM, Castillo EM, et al. Ketamine use for acute agitation in the emergency department. J Emerg Med. 2015;48:712-719.

8.  Schaeffer TH, Kralik KS, Strout TD The Use of Ketamine for Agitated Patients in the Prehospital Setting: A Systematic Review of the Literature Clin Tox

9.  Le Cong, M, Humble I. A Ketamine Protocol and Intubation Rates for Psychiatric Air Medical Retrieval Air Med J. 2015 Nov-Dec;34(6):357-9.

10.  Isbister GK, Calver LA, Downes MA, Page CB. Ketamine as Rescue Treatment for Difficult-to-Sedate Severe Acute Behavioral Disturbance in the Emergency Department. Ann Emerg Med. 2016 Feb 10.

11.  Kowalski JM, Kopec KT, Lavelle J, Osterhoudt K. A Novel Agent for Management of Agitated Delirium A Case Series of Ketamine Utilization in the Pediatric Emergency Department. Pediatr Emerg Care. 2015 Oct 13. 

12. Hopper AB et al.  Ketamine use for acute agitation in the emergency department.  J Emerg Med. 2015 Jun;48(6):712-9

13.  Lahti AC1, Koffel B, LaPorte D, Tamminga CA.  Subanesthetic doses of ketamine stimulate psychosis in schizophrenia.  Neuropsychopharmacology. 1995 Aug;13(1):9-19.