Etomidate is one of the most commonly used induction agents for:

• Rapid Sequence Intubation (RSI)

• Short procedural sedation (e.g., cardioversion)

Its appeal lies in:

• Rapid onset (10–20 sec)

• Short duration (4–10 min)

• Minimal cardiovascular depression

This makes it particularly valuable in critically ill or hypotensive patients, where even small drops in blood pressure can be dangerous.

Dosing essentials

• RSI: 0.3 mg/kg IV (max ~40 mg)

• Unstable / elderly: 0.2 mg/kg

• Procedural sedation: 0.1 mg/kg

Always dose using actual body weight to avoid awareness during paralysis.

Clinical advantages

• Preserves hemodynamic stability better than most induction agents

• Maintains cerebral perfusion pressure → useful in head injury

• Reliable intubating conditions with high first-pass success

• Rapid recovery profile for short procedures

Adrenal suppression: the central controversy

Mechanism

Etomidate inhibits 11β-hydroxylase, impairing cortisol synthesis:

• Leads to reduced endogenous cortisol production

• Effect occurs even after a single dose

Duration:

• Suppression may last 6–72 hours

Biochemical vs clinical significance

• Biochemical suppression:
  Almost universal → low cortisol levels after administration

• Clinical adrenal insufficiency:
  Variable → may present as:

  • Persistent hypotension

  • Increased vasopressor requirement

Key point:
Not all patients with low cortisol develop clinically significant instability.

Adrenal effects in real-world ED practice

In the emergency setting, etomidate-induced adrenal suppression is best understood as a transient physiologic trade-off rather than a definitive clinical harm.

While cortisol levels drop predictably after a single dose, most patients do not manifest overt adrenal crisis.

The effect becomes clinically relevant primarily in septic shock, where endogenous cortisol is crucial for maintaining vascular tone and catecholamine responsiveness.

In such patients, etomidate may contribute to vasopressor dependence or delayed shock reversal, even though a clear increase in mortality has not been consistently demonstrated. In contrast, in undifferentiated shock or cardiogenic instability, the immediate hemodynamic stability provided during intubation often outweighs this transient endocrine effect, making etomidate a reasonable and frequently preferred choice.

What the evidence shows

General ED population

• No consistent increase in mortality after single-dose use

• Benefits in maintaining hemodynamics often outweigh risks

Sepsis and septic shock

• Higher rates of adrenal suppression

• Increased vasopressor requirement seen in several studies

• No clear mortality difference compared with alternatives

Interpretation:

• The signal is physiologic (pressor need) rather than definitively outcome-driven

Other important adverse effects

• Myoclonus (~30%) → limits use in procedural sedation

• No analgesia → must combine with appropriate agents

• Transient apnea/hypoventilation possible

• Injection site pain (~20%)

• Avoid repeat dosing

Etomidate vs Ketamine: bedside decision-making

Outcomes between agents are largely similar—choice depends on physiology and context rather than superiority

Steroids after etomidate?

• Routine steroid use is not recommended

• No clear improvement in outcomes

• Reserve steroids for established refractory septic shock, not prophylaxis

Practical ED approach

Use etomidate when:

• Patient is hemodynamically unstable

• Concern for peri-intubation hypotension

• Need for neuroprotection

Consider alternatives when:

• Septic shock with high vasopressor requirement

• Concern for adrenal insufficiency impact

Take-home message

• Etomidate provides rapid, reliable, hemodynamically stable induction

• It causes predictable, transient adrenal suppression

• Clinical impact is usually limited, but context matters in sepsis

• The decision is not about the drug alone—it’s about the patient in front of you

“Etomidate protects the pressure upfront—just be mindful of the cortisol trade-off.”

1️⃣ Ketamine for Acute Pain (Sub-dissociative Dosing)

IV Analgesia

• 0.1–0.3 mg/kg IV infusion over 15–30 min

• Repeat in 1–2 hours if needed

• Consider infusion 0.05–0.25 mg/kg/h for ongoing pain
  (Engstrom et al., 2025)

  Ketamine _ CorePendium

What’s new:
Recent ED trials confirm that ~0.3 mg/kg IV provides comparable analgesia to opioids with fewer respiratory events (Beaudrie-Nunn et al., 2023; Lovett et al., 2020). Infusion is preferred over rapid IV push to reduce dizziness and psychoperceptual effects (Engstrom et al., 2025)

Alternative Routes

• Intranasal: 0.75–1 mg/kg

• Nebulized: 0.75–1 mg/kg
  (Engstrom et al., 2025)

  Ketamine _ CorePendium

Clinical Pearl: Excellent option when IV access is delayed (pediatrics, trauma, behavioral emergencies).

2️⃣ Procedural Sedation (PSA)

IV Dissociative Sedation

• 1 mg/kg IV, repeat 0.5 mg/kg as needed
  (Engstrom et al., 2025)

  Ketamine _ CorePendium

IM Dissociation

• 4–5 mg/kg IM

• Repeat 2–5 mg/kg if required
  (Engstrom et al., 2025)

  Ketamine _ CorePendium

Pediatric Safety Update

• Large pediatric ED registry: critical AEs 0.016%

• Meta-analysis (8,282 children): airway events increase with ≥2.5 mg/kg IV initial dose or ≥5 mg/kg total dose
  (Green et al., 2009; Green et al., 2025)

Emerging trend (2024–2025):

• Moderate dosing (0.5–1 mg/kg IV) achieves adequate sedation with fewer adverse effects than higher dosing (Türkücü et al., 2025).

• Structured sedation programs significantly reduce complications (Erumbala et al., 2023).

3️⃣ Acute Agitation & Behavioral Emergencies

IM for Severe Agitation

• 3–4 mg/kg IM initial agent

• 2 mg/kg IM if adjunctive or sedative intoxication
  (Engstrom et al., 2025)

  Ketamine _ CorePendium

IV (if access available)

• 1–2 mg/kg IV (less well studied for agitation)

Key Updates:

• ED airway intervention rates are significantly lower than early EMS reports when dosing is standardized (Mankowitz et al., 2018; Kwong et al., 2025).

• Avoid polypharmacy with opioids or benzodiazepines unless clinically indicated — airway events increase with co-administration.

4️⃣ Airway Management: RSI, DSI & Post-Intubation

RSI Induction

• 1–2 mg/kg IV push

• In shock: 0.5–1 mg/kg IV, titrate
  (Engstrom et al., 2025)

Delayed Sequence Intubation (DSI)

• ~1 mg/kg IV to achieve dissociation while preserving respirations
  (Merelman et al., 2019)

Post-Intubation Sedation

• Bolus 1–2 mg/kg

• Infusion 1–5 mg/kg/h

Hemodynamic Advantage:
Ketamine supports blood pressure via indirect sympathomimetic activity (Engstrom et al., 2025)

Important nuance (2025 update):
Higher induction doses (2 mg/kg) in shock have been associated with post-intubation hypotension — titrated dosing (0.5 mg/kg increments) is recommended

5️⃣ Status Asthmaticus

Non-intubated

• 0.5–1 mg/kg IV bolus

• 0.25–0.5 mg/kg/h infusion

Intubated

• Up to 0.75–3 mg/kg/h infusion

Bronchodilation is clinically useful, though meta-analyses show mixed outcome benefit (Engstrom et al., 2025)

6️⃣ Refractory Status Epilepticus

• 1–2 mg/kg IV bolus

• 0.1–4 mg/kg/h infusion

• Continuous EEG recommended
  (Engstrom et al., 2025)

Ketamine’s NMDA antagonism is particularly valuable in late-phase refractory seizures.

7️⃣ Special Populations & Safety Pearls

Pregnancy

• Should not be withheld if clinically indicated

• Single ED dose unlikely to cause fetal harm
  (Engstrom et al., 2025)

Breastfeeding

• Avoid for 6–12 hours post-dose

Intracranial Pressure

• Contemporary data suggest ketamine does not increase ICP and may reduce it.

Adverse Effects to Anticipate

• Emergence reactions (10–20%)

• Laryngospasm - < 3 months (rare; manage with Larson maneuver)

• Increased secretions (consider glycopyrrolate 0.2 mg IV)

• Nausea/vomiting

  

📌 2026 Clinical Takeaways

1. Think in a dose continuum — analgesia (0.1 mg/kg) → dissociation (1 mg/kg) → airway control (1–2 mg/kg).

2. Moderate IV dosing (0.5–1 mg/kg) often balances efficacy and safety for PSA.

3. In shock, titrate (0.5 mg/kg increments) rather than reflexively giving 2 mg/kg.

4. Avoid unnecessary co-administration of respiratory depressants.

5. Pediatric safety remains excellent when high doses are avoided.

Ketamine remains one of the most hemodynamically stable induction agents in ED airway management.

References

1. Mirfazaelian H, Fazel A, Azizi N, et al. Non-injectable ketamine for pediatric sedation in the emergency department: a systematic review. Acad Emerg Med. 2025;32:1344-1355. doi:10.1111/acem.70163

2. Sharif S, Kang J, Sadeghirad B, et al. Pharmacological agents for procedural sedation and analgesia in the emergency department and intensive care unit: a systematic review and network meta-analysis of randomized trials. Br J Anaesth. 2024. doi:10.1016/j.bja.2023.11.050

3. Esmaillian M, Kouhestani S, Azizkhani R, et al. Dexmedetomidine versus propofol: an effective combination with ketamine for adult procedural sedation: a randomized clinical trial. Am J Emerg Med. 2023;73:95-101. doi:10.1016/j.ajem.2023.08.025

4. Türkücü Ç, Parlak I, Kokulu K, Sert E, Mutlu H. Comparison of the incidence of recovery agitation with two different doses of ketamine in procedural sedation: a randomized clinical trial. Acad Emerg Med. 2025;32:857-862. doi:10.1111/acem.15116

5. Ghojazadeh M, Sanaie S, Paknezhad S, et al. Using ketamine and propofol for procedural sedation of adults in the emergency department: a systematic review and meta-analysis. Adv Pharm Bull. 2019;9:5-11. doi:10.15171/apb.2019.002

6. De Vries L, Veeger N, Van Roon E, Lameijer H. Low-dose ketamine or opioids combined with propofol for procedural sedation in the emergency department: a systematic review. Eur J Emerg Med. 2023;30:244-251. doi:10.1097/MEJ.0000000000001046

7. Nasir H, Zahid M, Saleh M, et al. Use of ketamine, propofol and their combination (ketofol) for procedural sedation in emergency department: a review. Pak J Health Sci. 2023;4(02). doi:10.54393/pjhs.v4i02.539

8. Poonai N, Canton K, Ali S, et al. Intranasal ketamine for procedural sedation and analgesia in children: a systematic review. PLoS One. 2017;12:e0173253. doi:10.1371/journal.pone.0173253

9. Jamal D, Powell C. Paediatric procedural sedation in the emergency department: is ketamine safe? Arch Dis Child. 2020;106:120-124. doi:10.1136/archdischild-2019-318610

10. Dilip T, Chandy G, Hazra D, et al. The adverse effects of ketamine on procedural sedation and analgesia in the emergency department. J Fam Med Prim Care. 2021;10:2279-2283. doi:10.4103/jfmpc.jfmpc_2140_20

11. M S, S J, A B, et al. A randomized controlled trial comparing ketamine versus fentanyl for procedural sedation in the emergency department for adults with isolated extremity injury. Malays Orthop J. 2024;18:116-124. doi:10.5704/moj.2403.015

12. Elsaeidy A, Ahmad A, Kohaf N, et al. Efficacy and safety of ketamine-dexmedetomidine versus ketamine-propofol combination for periprocedural sedation: a systematic review and meta-analysis. Curr Pain Headache Rep. 2024;28:211-227. doi:10.1007/s11916-023-01208-0

13. Anoumandane A, Murugesan V, Jayabalan K, et al. Comparison of ketamine-dexmedetomidine and ketamine-propofol for procedural sedation in adults – a single-center prospective randomized control study. Asian J Med Sci. 2025. doi:10.71152/ajms.v16i10.4770

14. Dehne L, Foertsch M, Bradshaw P, et al. Evaluation of subdissociative-dose ketamine for procedural sedation in the emergency department. Crit Care Med. 2022. doi:10.1097/01.ccm.0000908972.43680.39

15. Rached-d’Astous S, Finkelstein Y, Bailey B, et al. Intranasal ketamine for procedural sedation in children: an open-label multicenter clinical trial. Am J Emerg Med. 2023;67:10-16. doi:10.1016/j.ajem.2023.01.046

16. Erumbala G, Anzar S, Deiratany S, et al. Procedural sedation programme minimising adverse events: a 3-year experience from a tertiary paediatric emergency department. Arch Dis Child. 2023;109:88-92. doi:10.1136/archdischild-2023-326021

17. Strayer RJ, Nelson LS. Adverse events associated with ketamine for procedural sedation in adults. Am J Emerg Med. 2008;26:985-1028. doi:10.1016/j.ajem.2007.12.005

18. Green SM, Roback MG, Krauss B, et al. Predictors of airway and respiratory adverse events with ketamine sedation in the emergency department: an individual-patient data meta-analysis of 8,282 children. Ann Emerg Med. 2009;54:158-168.e1-4. doi:10.1016/j.annemergmed.2008.12.011

19. Green SM, Tsze DS, Roback MG. Emergency department ketamine sedation: frequency and predictors of critical and high-risk adverse events. Ann Emerg Med. 2025. doi:10.1016/j.annemergmed.2025.05.003

20. White N, Wendt W, Drendel A, Walsh P. Sedation with ketamine, propofol, and dexmedetomidine in pediatric emergency departments. Am J Emerg Med. 2025;93:21-25. doi:10.1016/j.ajem.2025.03.027

21. Merelman AH, Perlmutter MC, Strayer RJ. Alternatives to rapid sequence intubation: contemporary airway management with ketamine. West J Emerg Med. 2019;20:466-471. doi:10.5811/westjem.2019.4.42753

22. Mankowitz SL, Regenberg P, Kaldan J, Cole JB. Ketamine for rapid sedation of agitated patients in the prehospital and emergency department settings: a systematic review and proportional meta-analysis. J Emerg Med. 2018;55:670-681. doi:10.1016/j.jemermed.2018.07.017

23. Kwong J, Verbeek PR, Leong Y, et al. Paramedic use of ketamine for severe agitation and violence. Can J Emerg Med. 2025;27:653-660. doi:10.1007/s43678-025-00963-w

24. Beaudrie-Nunn A, Wieruszewski E, Woods E, et al. Efficacy of analgesic and sub-dissociative dose ketamine for acute pain in the emergency department. Am J Emerg Med. 2023;70:133-139. doi:10.1016/j.ajem.2023.05.026

25. Lovett S, Reed T, Riggs R, et al. A randomized, noninferiority, controlled trial of two doses of intravenous subdissociative ketamine for analgesia in the emergency department. Acad Emerg Med. 2020;28. doi:10.1111/acem.14200

26. Engstrom K, Nordt SP, Acquisto NM, Won K, Rech MA, Swadron S, Mattu A. Ketamine. In: CorePendium. EM:RAP; Updated August 2, 2025.

    Ketamine _ CorePendium