Pharmacology
- Mechanism
- NMDA receptor antagonist
- Multiple other receptors
| Drug | Onset (IM) | Onset (IV) |
| Ketamine1.5-2 mg/kg IV3-5 mg/kg IM | 1-2 min | 3-5 min |
- Dosage forms
- 50 mg/mL (10 mL), 100 mg/mL (5 mL)
- Administration
- IV – slow IV push (3-5 min) to avoid apnea
- IM – anterior aspect of thigh, though other sites are okay as well
- Effects
- Dissociative state 🡪 analgesia, amnesia
- Adverse Effects
- Tachycardia, hypertension, hypersalivation, vomiting, laryngospasm
Pros and Cons
Pros
- Rapid onset when given IM
- Wide therapeutic window
- Isbister et al, 2017
- Combination of antipsychotic with benzodiazepine results in increased respiratory depression than monotherapy
- Presence of alcohol (70% in this study and others) can result in worse respiratory depression
- Isbister et al, 2017
Cons
- Emergence reactions
- Laryngospasm
- Respiratory depression*
- Catecholamine release*
- Myocardial depressant?
- Drug shortages?
Studies
| Author | Patients | Methods | Findings |
| Cong, 2011Ketamine 0.5-1 mg/kg IV x 2 🡪 1-1.5 mg/kg/hr | N = 18 ptsAustralian prehospital flight transport protocol | Retrospective review | 1 incidence of vomitingNo airway interventionNo worsening agitation or psychiatric sx |
| Hopper, 2015Ketamine at various dosages IV or IM | N = 27 pts, 32 encounters41% EtOH or other substances62% additional meds | Retrospective review | No emergence reactionsNo worsening psychiatric sxNo hypoxiaTransient tachycardia/hypertension |
| Isbister, 2016Ketamine 4-6 mg/kgMedian 300 mg | N = 49 ptsFailed droperidol 10 mg IM x 2 doses | Subset analysis of prospective observational study | 44 of 49 pts adequately sedatedOf 5 pts who were not, dose < 200 mg1 incidence of SpO2 < 90% |
| Cole, 2017Ketamine 5 mg/kg IM | N = 158 ptsPrehospital protocol for combative and violent patients | Prospective observational, no comparator group | 90% achieved adequate sedation57% intubated upon arrival to ED80% intubated for < 24 hrsMajority overnight by single physician |
| Sullivan, 2019Review of ketamine for excited delirium | N = 13 studies | Systematic review | 85% achieved adequate sedation20% “airway management”0-63% intubated🡪 Heterogeneity in setting, dose |
| Mo et al, 2019Review of ketamine 3-5 mg/kg IM | N = 37 ptsSevere agitation, excited delirium, violent/self-destructive | Retrospective review | 16% had ”respiratory adverse event”3% intubated (seizures)15% either NC or nonrebreather |
Controversies
- Klein et al 2021
- Ketamine in the media
- Administered by Aurora EMS during police stop of Elijah McClain, who suffered cardiac arrest and was declared brain death
- Ketamine used as an adjunct to law enforcement and concerns of racial profiling in Hennepin county in Minnesota
- Ketamine in the media
“…the police had no legal basis to make McClain stop walking, to frisk him, or to use a chokehold and the paramedics failed to properly evaluate him – or even to attempt to speak with him – before injecting him with ketamine.”
- Airway reflexes
- Respiratory depression and apnea can still occur
- Additional respiratory depressants
- Rapid IV administration
- Respiratory depression and apnea can still occur
- Myocardial depressant?
- Catecholamine reuptake inhibition
“…it seems inevitable that rare cases of serious cardiovascular complications, including cardiac arrest, will occur”
Single Center Experience
- Setting
- Downtown San Diego
- Level 1 Trauma Center, Stroke Center, STEMI Receiving Center
- > 70,000 annual visits
- Study Design
- Prospective, single-institution, randomized, non-blinded study
- 80% power to determine a 30% difference 🡪 goal of 100 patients
- Methods
- Inclusion
- Adult patients with active diagnosis of combative agitation
- Exclusion
- Any known exclusion criteria to ketamine
- Pregnancy, schizophrenia, angina, uncontrolled hypertension CHF, etc
- Any known exclusion criteria to ketamine
- Endpoints
- Primary = adequate sedation within 5 minutes (RASS ≤ 0)
- Secondary = adequate sedation within 15 minutes, time to sedation, safety
- Inclusion
- Enrollment
- ED physicians screened/enrolled patients
- ED physicians/pharmacists randomized patients
- Randomization
- Computer-generated random number tables posted in each pod
- January 15, 2018 to October 10, 2018
Single Center Experience – Efficacy
Single Center Experience – Safety
Single Center Experience – Conclusions
- Ketamine was significantly more effective than haloperidol/lorazepam at adequately sedating patients within 5 minutes
- Significantly more patients adequately sedated within 15 minutes
- Significantly shorter time to sedation
- Ketamine was associated with a significant, but transient hypertension and tachycardia compared to haloperidol/lorazepam
- Possible signal for respiratory depression when used in intoxicated patients
The Ideal Medication…
- Administer IV or IM 🡪 recognize dosing differences
- Wide therapeutic window 🡪 in the ideal patient*
- Rapid onset 🡪 yes
- Consistent effect 🡪 yes
- No respiratory depression 🡪 yes*
- No other untoward adverse effects 🡪 kind of
- No exacerbation of underlying disease states 🡪 yes*
- Delirium, Parkinson’s disease
- No interaction with other medications/intoxications 🡪 kind of
- Home antipsychotics, co-ingestion of alcohol, opioids, sympathomimetics
- No drug shortages 🡪
- Generic and $$ 🡪 yes
- No respiratory depression 🡪 yes*
- No co-ingestants, IM or slow IVP administration
- No other untoward adverse effects 🡪 kind of
- No exacerbation of underlying disease states 🡪 yes*
- Hypersalivation 🡪 atropine
- Low incidence of emergence, laryngospasm, vomiting, psychiatric sx
- No interaction with other medications/intoxications 🡪 kind of
- co-ingestion of alcohol, opioids, sympathomimetics
- Alcohol/opioids 🡪 respiratory depression
- Sympathomimetics 🡪 sympathetic surge, cardiac arrest
- co-ingestion of alcohol, opioids, sympathomimetics