Ketamine | Medication Reference

Bedside Snapshot

Dissociative anesthetic with unique profile: Provides amnesia, analgesia, and catalepsy while usually preserving airway reflexes and spontaneous respirations at dissociative doses. Sympathomimetic (↑HR, ↑BP) via catecholamine release – useful in hemodynamically fragile patients compared with many other sedatives.
Main ED/ICU uses: (1) RSI induction and peri-intubation analgesia/sedation, (2) procedural sedation, (3) sub-dissociative ("analgesic-dose") ketamine for acute pain, (4) continuous infusions for analgesia/sedation in shock, and (5) high-dose dissociative infusions for refractory agitation/pain when other sedatives are limited by hypotension.
Sub-dissociative (analgesic) IV dosing: ~0.1–0.3 mg/kg IV over 5–15 minutes (or 0.1–0.3 mg/kg IV push in some ED protocols) with optional infusion 0.1–0.3 mg/kg/hour. Provides NMDA blockade and opioid-sparing analgesia with minimal hemodynamic compromise.
Dissociative sedation for procedures: Typically 1–2 mg/kg IV (given over ~30–60 seconds) OR 4–5 mg/kg IM, titrated to effect. Many ED/ICU clinicians instead use repeated 0.5–1 mg/kg IV boluses or 25–50 mg aliquots to the desired depth of dissociation.
RSI induction: 1–2 mg/kg IV push (ideal or adjusted body weight) is common for induction, often paired with a paralytic. Lower doses (e.g., 0.5–1 mg/kg) may be used in profound shock with ongoing post-intubation sedation/analgesia planned.
ICU analgesia/sedation: Low-dose infusion 0.1–0.5 mg/kg/hour (sometimes up to 1 mg/kg/hour) as an adjunct opioid-sparing analgesic or sedative in intubated patients; higher doses (1–5 mg/kg/hour) can produce continuous dissociation when other sedatives are not tolerated hemodynamically.
Key adverse effects: Hypersalivation, emergence reactions (vivid dreams, hallucinations, dysphoria), nausea/vomiting, transient tachycardia and hypertension. At high doses or with co-sedatives, can still cause airway obstruction and hypoventilation.

Brand & Generic Names

Generic Name: Ketamine hydrochloride
Brand Names: Ketalar, various generics; many institution-specific premixed infusions

Medication Class

Dissociative anesthetic; NMDA receptor antagonist; analgesic, sedative, and bronchodilator with sympathomimetic properties

Pharmacology

Mechanism of Action:

Noncompetitive NMDA receptor antagonist: Blocks the phencyclidine (PCP) site within the NMDA receptor channel, reducing excitatory glutamatergic transmission and central sensitization to pain
Also interacts with opioid receptors (μ, κ), monoaminergic receptors, voltage-gated calcium channels, and HCN channels, contributing to analgesia and mood effects
Produces dissociative anesthesia by functionally uncoupling the thalamocortical and limbic systems: patients appear awake (eyes open, preserved corneal reflexes) but are amnestic and unresponsive to painful stimuli
Sympathomimetic effects result from inhibition of neuronal catecholamine reuptake and increased endogenous catecholamine release, usually increasing HR and BP in patients with intact catecholamine stores
At very high doses or in catecholamine-depleted patients (e.g., prolonged shock), direct myocardial depressant effects can emerge and hypotension may occur

Pharmacokinetics (IV/IM):

Routes: IV, IM, intranasal, oral, subcutaneous. ED/ICU usage is primarily IV and IM; intranasal is used in some pediatric and prehospital protocols
Onset: IV – 30 seconds for dissociation; peak effect within 1 minute. IM – onset ~3–5 minutes with peak ~5–15 minutes. IN – onset ~5–10 minutes
Duration: Dissociative effect of a single IV dose usually 10–20 minutes; IM 20–30 minutes, with longer recovery due to redistribution. Sub-dissociative doses provide analgesia for 30–60+ minutes
Distribution: Highly lipophilic with rapid CNS penetration; large volume of distribution (~3 L/kg)
Metabolism: Primarily hepatic CYP2B6 and CYP3A4 to norketamine (active, ~1/3 potency) and further metabolites; conjugated and renally excreted
Elimination Half-Life: ~2–3 hours, but clinical effects dissipate sooner because of redistribution from the CNS to peripheral tissues
Special Considerations: Hepatic impairment and prolonged infusions can lead to accumulation and prolonged recovery; adjust doses and allow longer weaning intervals

Indications

Rapid sequence intubation (RSI) induction, especially in hypotensive or asthmatic patients where ketamine's sympathomimetic and bronchodilatory properties are beneficial
Procedural sedation for painful procedures (fracture reduction, cardioversion, laceration repair, chest tube insertion, DCCV, etc.)
Sub-dissociative (analgesic-dose) ketamine for acute pain (trauma, abdominal pain, renal colic, vaso-occlusive crisis) as opioid-sparing therapy
Continuous infusion for analgesia/sedation in mechanically ventilated patients, especially when hypotension limits use of propofol or dexmedetomidine
Adjunct in refractory status asthmaticus (bronchodilation) and refractory status epilepticus (NMDA blockade) – typically under intensivist/neurology guidance
Off-label: treatment-resistant depression and suicidality (usually in structured outpatient programs; not the focus of this ICU/ED reference)

Dosing & Administration

Available Forms:

Injectable solution: 10 mg/mL, 50 mg/mL, 100 mg/mL vials
Institution-specific premixed infusions for continuous sedation
Available for IV, IM, intranasal, oral, and subcutaneous routes (ED/ICU primarily uses IV and IM)

Dosing – Common ED/ICU Uses (Adult, Always Follow Local Protocol):

Indication	Typical Dose	Route	Notes
Analgesic (sub-dissociative) dosing for acute pain	0.1–0.3 mg/kg IV over 5–15 min; optional infusion 0.1–0.3 mg/kg/h	IV	Can be given as slow IV push; watch for dysphoria, nausea
Dissociative procedural sedation – IV	1–2 mg/kg IV over 30–60 sec (or repeated 0.5–1 mg/kg boluses)	IV	Titrate to dissociation; premedicate for secretions as needed
Dissociative procedural sedation – IM	4–5 mg/kg once	IM	Useful when IV access is difficult; slower onset and longer recovery
RSI induction	1–2 mg/kg IV push	IV	Consider lower dose (0.5–1 mg/kg) in profound shock
ICU analgesia/sedation infusion	0.1–0.5 mg/kg/h (up to ~1 mg/kg/h); dissociation at 1–5 mg/kg/h	IV infusion	Always combine with analgesia/sedation strategy and monitoring
Status asthmaticus / refractory bronchospasm (adjunct)	0.5–1 mg/kg IV bolus, then 0.5–1 mg/kg/h infusion	IV	Evidence limited; use under intensivist guidance

Contraindications

Contraindications (Relative/Absolute – Context Matters):

Known ketamine hypersensitivity
Situations where a transient rise in BP/HR or ICP is hazardous (e.g., uncontrolled hypertension, aortic dissection, certain intracranial pathologies) – though ICP concerns are increasingly debated
Severe or uncontrolled coronary disease or aortic pathology where tachycardia/hypertension could be dangerous
History of severe psychosis or schizoaffective disorder – risk of worsening psychosis/emergence reactions (relative; may still be used in life-threatening situations)

Major Precautions:

Emergence phenomena: Hallucinations, vivid dreams, agitation – more common in adults and higher doses; consider benzodiazepine co-medication or calm environment
Hypersalivation: May require antisialagogue (e.g., glycopyrrolate); excessive secretions can increase risk of laryngospasm
Cardiovascular: Monitor BP/HR closely; in catecholamine-depleted shock, direct myocardial depression may predominate and hypotension can occur
Increased ICP/IOP: Historical concern; current data suggest effects are modest and context dependent, but caution is still advised in uncontrolled intracranial hypertension or open globe injury
Prolonged/high-dose infusions: Monitor liver function and urinary symptoms; chronic/recreational use has been associated with ulcerative cystitis and hepatotoxicity

Catecholamine-Depleted Shock: In patients with prolonged shock who are catecholamine-depleted, ketamine's direct myocardial depressant effects may predominate, potentially causing hypotension. Monitor closely and be prepared to support blood pressure.

Adverse Effects

Common:

Emergence reactions (vivid dreams, hallucinations, dysphoria)
Nausea, vomiting, dizziness
Tachycardia, hypertension, palpitations
Hypersalivation and increased airway secretions
Nystagmus, diplopia

Serious:

Laryngospasm (rare, more common with rapid bolus and in children)
Apnea or hypoventilation, especially with co-administered sedatives/opioids
Severe agitation or delirium requiring additional sedation
Rare anaphylaxis or severe hypersensitivity
Potential bladder dysfunction/ulcerative cystitis with long-term high-dose use
Hypotension in catecholamine-depleted shock states

Special Populations

Elderly Patients:

May have increased sensitivity to ketamine effects
Consider lower initial doses and slower titration
Monitor for emergence reactions and cardiovascular effects

Hemodynamically Unstable / Shock States:

Ketamine is often preferred over propofol or benzodiazepines due to sympathomimetic effects
Be aware that in severe catecholamine-depleted states, hypotension can still occur
Consider lower RSI doses (0.5–1 mg/kg) in profound shock

Asthma / Bronchospasm:

Ketamine is an excellent choice for RSI in asthmatic patients due to bronchodilatory effects
Can be used as adjunct in refractory status asthmaticus

Hepatic Impairment:

Prolonged infusions may lead to accumulation of ketamine and active metabolites
Consider dose reduction and extended weaning intervals
Monitor for prolonged recovery and sedation

Pregnancy & Lactation:

Pregnancy Category: Not formally classified; use with caution
May increase uterine tone; use in pregnancy only when benefits outweigh risks
Excreted in breast milk; consider temporary interruption of breastfeeding

Pediatric:

Widely used for procedural sedation in pediatrics
IM route (4–5 mg/kg) commonly used when IV access is difficult
Intranasal route (3–5 mg/kg) used in some protocols

Monitoring

Clinical Monitoring:

Continuous cardiorespiratory monitoring (ECG, NIBP/invasive BP, SpO₂, EtCO₂ if available) for any IV ketamine used for RSI, procedural sedation, or infusion
Level of consciousness and response to stimuli; ensure appropriate depth of sedation for procedures and post-intubation care
Airway patency, respiratory rate, and adequacy of ventilation; be prepared for suctioning and airway maneuvers
Hemodynamics (HR, BP) especially in patients with cardiovascular disease or shock – adjust dosing accordingly

For Prolonged Infusions:

Liver function tests
Urinary symptoms
Neuropsychiatric status

Emergence Phase:

Monitor for emergence reactions (hallucinations, agitation, dysphoria)
Maintain calm, quiet environment during recovery
Be prepared to treat severe emergence reactions with benzodiazepines

Clinical Pearls

Go Slow for Analgesia: For analgesic-dose ketamine, go slow (over 5–15 minutes) to reduce dysphoria and nausea. Adding a low-dose benzodiazepine or antiemetic can improve tolerability. This approach provides excellent opioid-sparing analgesia with minimal hemodynamic impact.

Perfect for Crashing Asthmatics: In the crashing asthmatic, ketamine is an excellent induction agent because it provides bronchodilation and tends to support BP. Pair with aggressive bronchodilator and steroid therapy. The sympathomimetic effects help maintain hemodynamics during intubation.

Don't Forget Post-Intubation Sedation: An induction dose of ketamine will wear off quickly (10–20 minutes). Start a continuous sedative/analgesic regimen early to prevent awareness and patient-ventilator dyssynchrony. Many providers use a ketamine infusion or transition to propofol/fentanyl.

Managing Emergence Reactions: If emergence reactions occur, small doses of midazolam (2–5 mg IV) or propofol are usually effective. Keep the environment calm and limit stimulation during recovery. Reassure the patient that the effects are temporary and will resolve.

Safer in Agitated Trauma: For agitated trauma or undifferentiated shock, ketamine often provides safer sedation than large benzodiazepine or propofol doses. However, watch for catecholamine-depleted states (prolonged shock, sepsis) where BP may fall due to direct myocardial depression.

ICP Concerns Overstated: Historical concerns about ketamine raising ICP have been challenged by recent evidence. In mechanically ventilated patients with controlled ventilation, ketamine appears safe even in traumatic brain injury. However, caution is still advised in uncontrolled intracranial hypertension.

Hypersalivation Management: Ketamine increases salivation, which can increase the risk of laryngospasm. Consider premedication with glycopyrrolate (0.1–0.2 mg IV) or atropine, especially in pediatric patients or when using higher doses. Have suction readily available.

Eyes-Open Dissociation: Patients in ketamine dissociation often have their eyes open with a blank stare, preserved corneal reflexes, and nystagmus. This can be disconcerting for staff and family. Explain that this is expected and does not indicate awareness or distress – the patient is amnestic and not processing external stimuli.

Opioid-Sparing Analgesia: Sub-dissociative ketamine (0.1–0.3 mg/kg) is excellent for opioid-sparing analgesia in the ED. It's particularly useful for renal colic, acute abdominal pain, trauma, and sickle cell crisis. Patients remain conversant and oriented, but pain is significantly reduced.

References

1. Peltoniemi, M. A., Hagelberg, N. M., Olkkola, K. T., & Saari, T. I. (2016). Ketamine: A review of clinical pharmacokinetics and pharmacodynamics in anesthesia and pain therapy. Clinical Pharmacokinetics, 55(9), 1059–1077. https://doi.org/10.1007/s40262-016-0383-6
2. Schwenk, E. S., Viscusi, E. R., Buvanendran, A., Hurley, R. W., Wasan, A. D., Narouze, S., Bhatia, A., Davis, F. N., Hooten, W. M., & Cohen, S. P. (2018). Consensus guidelines on the use of intravenous ketamine infusions for acute pain management from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Regional Anesthesia and Pain Medicine, 43(5), 456–466. https://doi.org/10.1097/AAP.0000000000000806
3. Green, S. M., Roback, M. G., Kennedy, R. M., & Krauss, B. (2011). Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Annals of Emergency Medicine, 57(5), 449–461. https://doi.org/10.1016/j.annemergmed.2010.11.030
4. Zeiler, F. A., Teitelbaum, J., West, M., & Gillman, L. M. (2014). The ketamine effect on ICP in traumatic brain injury. Neurocritical Care, 21(1), 163–173. https://doi.org/10.1007/s12028-013-9950-y
5. Motov, S., & Mai, M. (2018). Ketamine: The new "safe" sedative? Emergency Medicine News, 40(5), 1,16–17. https://journals.lww.com/em-news/