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Three Part Question

In [adult patients attending the emergency department with acute behavioural disturbance] is [ketamine] [safe and effective for sedation]?

Clinical Scenario

A 39-year-old female with acute behavioural disturbance was brought to the emergency department by police. She was intoxicated with alcohol, agitated, very abusive, spitting on others, and presented a physical threat to other patients and hospital personnel. Her relevant medical history was not known and it was not possible to take vital signs. She was physically restrained by five hospital security guards. You are concerned about the patient’s airway because of physical restraint, the possibility of cardiovascular instability and metabolic derangements, and about the safety of the emergency department environment. You wonder whether ketamine is an appropriate first drug of choice in this setting.

Search Strategy

A literature search was conducted using
1. Clinical Key
2. CINAHL
3. Cochrane Library Database
4. EMBASE
5. EBM Reviews Database
6. Emerald
7. ERIC
8. Medline Pub Med
9. Medline Ovid
10. Google Scholar
11. Reference of Selected papers were reviewed for other relevant articles
The following search string was used: (Ketamine) OR (Acute agitation) OR (Acute behavioural disturbance) OR (Excited delirium) OR (Excited delirium syndrome)

The following search string was used: (Ketamine) OR (Acute agitation) OR (Acute behavioural disturbance) OR (Excited delirium) OR (Excited delirium syndrome)

Search Outcome

In total, 3 papers were relevant to the three-part question

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Austin B. Hopper, Gary M. Vilke, Edward M. Castillo et al. 2015 USA	27 patients from two different EDs were administered ketamine for acute agitation during study period (from 15 Sept 04 until 6 Jun 12)	Retrospective observational study	Ketamine was used without any major adverse effects on vital signs, even in a population with 21.9% alcohol intoxication	No patients became hypoxic; the lowest oxygen saturation after Ketamine administration was 94%.	Study is limited by its sample size. A high proportion (62.5%) of patients required additional pharmacologic treatment for their agitation, implying that ketamine itself is not an ideal treatment for the underlying cause of agitation, but rather a means of initial management of severe agitation.
Isbister, Geoffrey Kennedy; Calver, Leonie A. et al. 2016 USA	49 patients from two different EDs were administered ketamine for acute agitation during the study period (from Dec 2011 until Feb 14).	Prospective observational study	Ketamine appeared effective and did not cause obvious harm in this small sample and is a potential option for patients who have failed attempts at sedation.	There were adverse effects in 3 patients (6%) treated with Ketamine. Two patients had vomiting and third had an episode of oxygen desaturation to 90%.	Study is limited by its sample size. Although ketamine administration was associated with no serious adverse events, larger samples would be required to reliably confirm its safety profile.
Jeff Riddell, Alexander Tran, Rimon Bengiamin et al. 2017 USA	24 of 98 patients from a single centre were administered ketamine for acute agitation: others had midazolam, lorazepam, haloperidol and combination(from May 2013 to Jan 2015)	Prospective observational study	Ketamine appears to be faster at controlling agitation than midazolam, lorazepam and haloperidol	Agitation score 5-, 10-, 15- mins. Agitation scores in Ketamine group decreased more rapidly (p = 0.001, p ≤ 0.001, P = 0.032).	This was a single centre study in population exhibiting a high percentage of methamphetamine abuse. Data may not be generalizable to populations with different toxicological profiles. This study is limited by its sample size. Although Ketamine administration had similar adverse events as other sedating medications, a larger sample is required to reliably confirm its safety profile.

Comment(s)

The best available evidence for the efficacy and safety of ketamine for initial management of acute behavioural disturbance is Level IV. Limitations of the included papers are observational design, small patient numbers, and lack of consistent, objective efficacy and safety outcomes across studies. These limitations in the published evidence should be considered by clinicians managing patients with this challenging condition.

Clinical Bottom Line

ketamine appears to be faster at controlling severe agitation than standard emergency department medications with no difference in reported safety outcomes

References

1. Austin B. Hopper, Gary M. Vilke, Edward M. Castillo, Ashleigh Campillo,Timothy Davie, Michael P. Wilson et al Ketamine use for acute agitation in the emergency department Journal of Emergency Medicine Jun2015; 48(6): 712-719
2. Isbister, Geoffrey Kennedy; Calver, Leonie A.; Downes, Michael A.; Page, Colin B. et al. Ketamine as Rescue Treatment for Difficult-to-Sedate Severe Acute Behavioural Disturbance in the Emergency Department Annals of Emergency Medicine May2016; 67(5): 581-587
3. Jeff Riddell,Alexander Tran, Rimon Bengiamin, Gregory W Hendey and Patil Armenian et al. Ketamine as a first-line treatment for severely agitated emergency department patients American Journal of Emergency Medicine 2015 Jun; 48(6):712-9