Ketamine for Treatment of Acute Agitation


  1. Ketamine is a sedative used for patients with extreme/refractory undifferentiated agitation
  2. Indications for utilizing ketamine for emergent sedation of agitated patients include
    • Patient poses and immediate threat to patient and healthcare provider safety (RASS +4)
    • Failure and/or futility of alternative non-pharmacologic de-escalation strategies
    • Absence of IV access
    • Not a candidate for intramuscular antipsychotics and/or benzodiazepines due to onset of action 


PropertiesRapid acting general anesthetic producing cataleptic-like state due to antagonism of N-methyl-Daspartate (NMDA) receptors in the central nervous system.         
•      Ketamine also has significant analgesic/dissociative properties at lower doses 
Dose2-5 mg/kg IM to a max single dose of 500mg
1-2 mg/kg IV  
AdministrationIM: Inject deep IM into large muscle (glute or vastus lateralis muscle)
IV: Administer over at least 60 seconds
Formulation10 mg/mL, 50 mg/mL, 100 mg/mL 
*must use 100 mg/mL for IM administration to reduce volume   
PK/PD (for amnestic effects)Onset: 3-5 mins IM;   <1 minutes IV
Duration: 15-25 mins IM;  5-10 minutes IV
Bioavailability: 93% IM
Metabolism: Extensively through hematic N-demethylation
Elimination: Greater than 90% urine, <5% feces 
Adverse EffectsHypertension
Nausea and vomiting 
Emergence phenomenon during  recovery phase
Increased muscle function  (hyperactivity, twitching, rigidity) 
Contraindications        •      Significant hypertension may be hazardous, ACS, ADHF, and unstable dysrhythmia
Warnings and ConsiderationsRapid IV administration may increase risk of respiratory depression/apnea
Verify concentration of formulation
Caution in diagnosed schizophrenia 
Hypotension in catecholamine depleted states
Pregnancy and lactation (crosses placenta)

Overview of Evidence

Author, yearDesign (sample size)Intervention & ComparisonOutcome
Lin et al., 2020Prospective, randomized, pilot (n=93)Ketamine 4 mg/kg IM or 1 mg/kg IV   Haloperidol 5-10 mg IM/IV +  lorazepam 1-2 mg IM/IVKetamine achieved greater sedation within 5 and 15 minutes (22% vs 0% at 5 mins; 66% vs 7% at 15 mins)
Mankowitz et al., 2018Systematic review (n=650)Ketamine IV or IMMean time to sedation was 7.21min and effective in 68.5% of patients 30.5% of patients required intubation, but not all secondary to ketamine administration
Cole et al., 2016Prehospital prospective, observational (n=146)  Haloperidol 10 mg IM   Ketamine 5 mg/kg IMMedian time to adequate sedation was faster with ketamine (5 min) vs haloperidol (17 min) • Intubation rates were higher with ketamine (39%) than haloperidol (4%), as well as more complications (49% vs 5%, respectively) 38% hypersalivation in ketamine group
Isbister et al., 2016Subgroup analysis from DORM II study; prospective, observational  (n=49)Ketamine as rescue treatment after Droperidol alone   Droperidol + DZP or MDZ   Midazolam aloneMedian time to sedation post-ketamine was 20 minutes (IQR 10-30) 3 patients had adverse reactions after ketamine (vomiting n=2; desaturation n=1)
Riddell  et al., 2016Prospective, observational  (n=106)Ketamine   Lorazepam, midazolam, haloperidol, or benzodiazepine + haloperidol Ketamine resulted in a greater number of patients with no agitation at 5 minutes than other medications
Scheppke  et al., 2014Retrospective chart review (n=52)Ketamine ~4mg/kg IM   *Recommended midazolam 2-2.5 mg IM or IV following ketamine for emergence reaction96% of patients obtained sedation, mean time to sedation was 2 minutes 3 patients experienced significant respiratory depression About ½ of patients received midazolam

Trials in Progress

Barbic et al., Completed March 2020, results pendingParallel, prospective, randomized, controlledKetamine 5mg/kg IM   Midazolam 5mg IM + haloperidol 5mg IMPrimary: Time to adequate sedation  Secondary: safety and tolerability, requirement of rescue medication
DZP= Diazepam; MDZ= Midazolam


  1. Ketamine has been shown to be effective with a quick time to sedation but is not without risks, including respiratory depression
  2. Used ketamine with caution in patients who have an underlying psychiatric disorder 
  3. Ketamine should be reserved for specific patient populations and as last line for patient/provider safety


  1. Ketamine. Micromedex [Electronic version].              
  2. Barbic D, et al. Trials. 2018;19(1):651. Published 2018 Nov 26.
  3. Lin M, et al. Am J Emerg Med. 2020. https://doi.org/10.1016/doi:10.1186/s13063-018-2992-x j.ajem.2020.04.013.
  4. Mankowitz WL, et al. J Emerg Med. 2018;55(5):670-81.
  5. Cole JB, et al. Clin Toxicol (Phila). 2016;54(7):556–562.
  6. Isbister GK, et al. Ann Emerg Med. 2016;67(5):581–587.
  7. Riddell J, et al. Am J Emerg Med. 2017. http://dx.doi.org/10.1016/j.ajem.2017.02.026
  8. Scheppke KA, et al. WestJEM. 2014;15(7);736-41.

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