Sedation of the agitated and aggressive patient is a frequently encountered problem in the Emergency Department (ED). Whether the etiology of the agitation is intoxication, psychiatric, or organic, these patients require quick and efficient chemical sedation because they are both a danger to themselves and others in the ED. The majority of these patients are successfully sedated with antipsychotics or benzodiazepines (Downes 2009).
A small number of these patients however, remain difficult to sedate despite multiple doses of medication (Calver 2012). One study showed only 8% of patients were not sedated after 1 or 2 doses of droperidol, and only 3% after 3 doses (Calver 2015). Although uncommon, these difficult –to-sedate patients consume considerable resources and time in the ED. Additionally, they pose continued threats to themselves as well as ED staff and other patients.
Escalating doses of benzodiazepines are a frequent first choice for difficult-to-sedate patients. However, there is some evidence that benzodiazepines alone and combinations of benzodiazepines and antipsychotics are associated with higher rates of adverse effects than antipsychotics alone (Isbister 2010, Calver 2015). Additionally, there exists a significant subset of patients who’s agitation is refractory to benzodiazepines due to abuse and cross tolerance. Ketamine may be a safer alternative.
There is limited data available on the sedation of acutely agitated patients in the ED that have been resistant to standard medications. Ketamine has been successfully used to sedate severely agitated out-of-hospital patients (Scheppke 2014, Le Cong 2012). Hopper 2015 found that ketamine could be used as an initial drug for sedation in the ED but that providers often required other medications afterwards. In this study however, the median dose of ketamine given was 200mg intramuscularly (IM).
Is ketamine a safe and effective rescue option for sedation in the acutely agitated patient in the ED?
Patients > 16 years old with acute behavioral disturbance recruited as part of the DORM II study that required physical restraint and parenteral sedation (had a score of 2 to 3 on the Sedation Assessment Tool) *see Appendix
Patients who remained agitated and aggressive after initial sedation and received ketamine as additional sedation
4-6 mg/kg of intramuscular ketamine administered as a third-line agent in patients being managed with a standardized sedation protocol (initial 10mg dose of intramuscular droperidol, second dose of 10mg droperidol if patient not sedated within 15 minutes)
Primary: The number of patients who failed to achieve sedation within 120 minutes of ketamine administration
Time to sedation from the initial onset of acute behavioral disturbance
Time to sedation after administration of ketamine
Any adverse effects (airway obstruction, oxygen saturation less than 90%, respiratory rate < 12 breaths/min, systolic blood pressure (SBP) less than 90 mmHg) Change in pulse rate and blood pressure after ketamine administration
Subgroup analysis of difficult-to-sedate patients with severe acute behavioral disturbance within an existing prospective observational study
Patients who were successfully de-escalated with verbal intervention or oral medication.
- Of 1296 patients sedated as part of the DORM II protocol at 2 hospitals in a 27-month period, 49 patients received ketamine after failure of previous sedation attempts
- Median dose of ketamine used was 300mg IM
- 5 patients (10%) were not sedated within 120 min, or required additional sedation within one hour
- Median time to sedation from onset of acute behavioral disturbance was 60 min
- Median time to sedation post ketamine was 20 min
- 3 (6%) patients had adverse effects after ketamine
- 2 patients had vomiting
- 1 patient had an episode of oxygen desaturation to 90% without airway obstruction 40 min after ketamine administration (responded to oxygen with no further problems)
- Median change of +5 mmHg in SBP measured at a median time of 15 min post administration
- No patients became hypotensive
- Median change of 0 beats/min between pre- and post- pulse rates
- 5 of 49 patients (10%) were not successfully sedated within 120 min of ketamine administration (n = 1), required additional medications at 60 minutes (n = 3) or both (n = 1)
- 3 (6%) patients had adverse effects after ketamine sedation:
- 2 patients experienced vomiting
- 1 patient desaturated to 90% but responded to only oxygen and did not have airway obstruction
- There was a median change of +5mm Hg in SBP 15 min post ketamine administration, no patients became hypotensive, and there was no median change in pulse rate in most patients
- Multicenter trial
- Study asked a clear clinical question that was realistically tested
- Looked at patient centered outcomes
- Minimal exclusions increased the applicability to ED patients
- Outcome measures were objectively measured using a standard sedation assessment tool reducing bias
- Observational trial. Ketamine was not compared to an alternative agent
- The primary outcome of sedation at 120 minutes is a suboptimal one. Optimally, we would like the patient sedated rapidly (< 10-20 minutes)
- Small sample size of patients receiving ketamine
- Not all patients received the same amount or type of sedation medication(s) prior to the use of ketamine as a rescue drug
- Droperidol is not commonly used in the US for sedation of the agitated patient limiting applicability of these results to US patients
- There was variability in the timing between droperidol doses and ketamine administration so it is not possible to determine whether the ultimate sedation of the patient was solely due to the ketamine or a delayed response of initial medication
- Study was a subgroup analysis from a study that was designed initially to assess droperidol
“Ketamine appeared effective and did not cause obvious harm in this small sample and is a potential option for patients who have failed previous attempts at sedation. A dose of 4 to 6 mg/kg is suggested, and doses less than 200 mg are associated with treatment failure.”
Ketamine appears to be an effective rescue sedation option for the difficult-to-sedate, acutely agitated patient in the ED. In this study only 10% of acutely agitated patients in the ED failed sedation with ketamine at 120 minutes. In addition, the majority of the patients that were not successfully sedated were likely under dosed (less than 4-6 mg /kg) per the study’s sedation protocol.
Side effects were low in this study but conclusions on safety cannot be made with this small of a study population. However, there are multiple other studies as well as significant clinical experience using ketamine for sedation without significant safety issues.
Potential Impact To Current Practice
IM ketamine is already frequently used in many EDs (particularly outside the US) for sedation of the acutely agitated patient. The data here is limited by a number of factors and doesn’t necessarily change practice.
IM ketamine may be considered an effective agent for sedation of the difficult -to-sedate, acutely agitated patient in the ED when dosed appropriately (4-6 mg/kg).
The Poison Review: Is Ketamine Safe and effective in excited delirium?
Green, SM. Let’s “Take ‘Em Down” with the ketamine blow dart. Ann Emerg Med. 2016 May; 67(5):588-90. PMID: 26899460
Downes MA. et al. Structured team approach to the agitated patient in the emergency department. Emerg Med Australas. 2009 Jun;21(3):196-202. PMID: 19527279