Introduction
Ketamine is a sedative used for patients with extreme or refractory undifferentiated agitation. When traditional de-escalation strategies fail and patient or provider safety is at immediate risk, ketamine offers a rapid-onset option for emergent sedation, particularly when IV access is unavailable.
Key Indications for Ketamine Sedation
- Patient poses an 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
Pharmacology of Ketamine
| Parameter | Details |
|---|---|
|
Mechanism of Action
|
Rapid acting general anesthetic producing cataleptic-like state due to antagonism of N-methyl-D-aspartate (NMDA) receptors in the central nervous system. Also has significant analgesic/dissociative properties at lower doses. |
|
Dose
|
IM: 2–5 mg/kg (max single dose 500 mg) IV: 1–2 mg/kg |
|
Administration
|
IM Inject deep IM into large muscle (glute or vastus lateralis) IV Administer over at least 60 seconds |
|
Formulation
|
10 mg/mL, 50 mg/mL, 100 mg/mL *Must use 100 mg/mL for IM administration to reduce volume |
|
PK/PD
|
Onset: IM 3–5 min; IV <1 min
Duration: IM 15–25 min; IV 5–10 min
Bioavailability: 93% IM
Elimination: >90% urine, <5% feces
|
|
Adverse Effects
|
Hypertension
Tachycardia
Hypersalivation
Nausea/Vomiting
Laryngospasm
Emergence Phenomenon
Increased Muscle Tone
|
|
Contraindications
|
Hazardous with: Significant hypertension, ACS, ADHF, and unstable dysrhythmia |
|
Warnings
|
Rapid 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) |
Clinical Pearl
Ketamine should be reserved for specific patient populations and as a last line for patient/provider safety. Always use the 100 mg/mL concentration for IM dosing to minimize injection volume.
Overview of Key Evidence
| Author / Year | Design (n) | Intervention | Key Findings |
|---|---|---|---|
| Lin et al., 20203 |
RCT (Pilot)
n=93 |
Ketamine 4 mg/kg IM or 1 mg/kg IV vs haloperidol 5–10 mg IM/IV + lorazepam 1–2 mg IM/IV |
Greater sedation at 5 & 15 min
22% vs 0% at 5 min; 66% vs 7% at 15 min |
| Mankowitz et al., 20184 |
Systematic Review
n=650 |
Ketamine IV or IM |
Mean sedation 7.21 min
68.5% effective
30.5% intubation (not all ketamine-related) |
| Cole et al., 20165 |
Observational
n=146 |
Prehospital: haloperidol 10 mg IM vs ketamine 5 mg/kg IM |
Faster sedation: 5 min vs 17 min
Higher intubation (39% vs 4%), 38% hypersalivation |
| Isbister et al., 20166 |
Observational
n=49 |
Ketamine as rescue after droperidol alone, droperidol + BZD, or midazolam alone |
Sedation in 20 min (IQR 10–30)
3 adverse reactions (vomiting n=2; desaturation n=1) |
| Riddell et al., 20167 |
Observational
n=106 |
Ketamine vs lorazepam, midazolam, haloperidol, or BZD + haloperidol | More patients with no agitation at 5 min |
| Scheppke et al., 20148 |
Retrospective
n=52 |
Ketamine ~4 mg/kg IM; midazolam 2–2.5 mg IM/IV recommended post-ketamine |
96% sedation achieved
Mean 2 min to sedation
3 pts with significant respiratory depression |
Clinical Conclusions
Bottom Line
Ketamine achieves rapid sedation in acutely agitated patients but carries risks including respiratory depression. It should be reserved for specific patient populations and used as a last-line option for patient/provider safety.
Ketamine has been shown to be effective with a quick time to sedation but is not without risks, including respiratory depression.
Use ketamine with caution in patients who have an underlying psychiatric disorder.
Ketamine should be reserved for specific patient populations and as last line for patient/provider safety.
Full Reference List
- Ketamine. Micromedex [Electronic version].
- Barbic D, et al. Trials. 2018;19(1):651. Published 2018 Nov 26.
- Lin M, et al. Am J Emerg Med. 2020. https://doi.org/10.1016/j.ajem.2020.04.013.
- Mankowitz WL, et al. J Emerg Med. 2018;55(5):670–81.
- Cole JB, et al. Clin Toxicol (Phila). 2016;54(7):556–562.
- Isbister GK, et al. Ann Emerg Med. 2016;67(5):581–587.
- Riddell J, et al. Am J Emerg Med. 2017. http://dx.doi.org/10.1016/j.ajem.2017.02.026.
- Scheppke KA, et al. WestJEM. 2014;15(7):736–41.
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