Ketamine in Emergency Medicine: Dosing and Clinical Applications

Ketamine holds a unique position in emergency medicine. Few other drugs combine so many clinically relevant properties in a single agent: potent analgesia, dissociative anesthesia, bronchodilation, hemodynamic stability, and preservation of spontaneous breathing and protective reflexes – at least in many clinical scenarios. Whether in the trauma bay, on the emergency physician response vehicle, during anesthesia induction in the hemodynamically unstable patient, or for analgesia in entrapped trauma patients: ketamine is one of the medications you should confidently master as an emergency medicine provider. This article provides you with a systematic overview of pharmacology, indication-specific dosing, contraindications, and management of side effects.

Pharmacological Basics

Ketamine is a phencyclidine derivative that acts primarily as a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. This mechanism explains the so-called dissociative anesthesia: a functional disconnection between thalamocortical and limbic systems, leading to analgesia, amnesia, and a cataleptic state – with largely preserved protective reflexes and spontaneous breathing.

Mechanisms of Action Overview

• NMDA receptor antagonism: Primary mechanism for analgesia and dissociation
• Opioid receptor interaction: Contribution to analgesic effect (μ and κ receptors)
• Monoamine reuptake inhibition: Sympathomimetic effect through inhibition of norepinephrine and serotonin reuptake
• Sodium channel blockade: Local anesthetic effect at higher concentrations
• Bronchodilation: Direct relaxation of bronchial smooth muscle as well as sympathomimetically mediated

Pharmacokinetics

After intravenous administration, onset of action occurs within 30–60 seconds; after intramuscular administration within 3–5 minutes. The duration of action after IV bolus is approximately 10–20 minutes for anesthesia, while the analgesic effect lasts longer. Ketamine is hepatically metabolized via cytochrome P450 enzymes (primarily CYP3A4 and CYP2B6). The active metabolite norketamine possesses approximately one-third of the potency of the parent compound.

Racemic Mixture vs. S-Ketamine

In Austria and Germany, both the racemic mixture (ketamine) and the S-enantiomer (esketamine) are available. S-ketamine has approximately twice the analgesic and anesthetic potency of the racemic mixture. All dosages listed below refer to the racemic mixture – when using S-ketamine, the dose should be halved accordingly.

Indications and Dosing

Analgesia

Ketamine at subdissociative doses is an excellent option for analgesia, particularly in hemodynamically compromised patients where opioids may be problematic.

• Dosing IV: 0.1–0.3 mg/kg as a bolus, injected slowly over 1–2 minutes
• Dosing IN (intranasal): 0.5–1 mg/kg (good option when IV access is difficult)
• Dosing IM: 0.5–1 mg/kg
• Repeat dosing: As needed every 15–20 minutes, individual boluses of 0.1–0.15 mg/kg IV
• Continuous infusion: 0.1–0.3 mg/kg/h (e.g., as opioid-sparing co-analgesia)

Clinical tip: Slow injection over at least 60 seconds significantly reduces psychomimetic side effects. A too-rapid bolus frequently leads to unpleasant dysphoric episodes.

Anesthesia Induction (Rapid Sequence Induction)

Ketamine is the induction agent of choice in the hemodynamically unstable patient. The sympathomimetic effect stabilizes blood pressure and heart rate – a decisive advantage over propofol or thiopental in shock.

• Dosing IV: 1–2 mg/kg as a bolus
• Dosing IM (if no IV access): 4–6 mg/kg
• Combination agents: Always with a neuromuscular blocking agent (e.g., rocuronium 1–1.2 mg/kg) during RSI

Typical scenarios for ketamine as an induction agent:

• Hemorrhagic shock / polytrauma
• Septic shock with hemodynamic instability
• Status asthmaticus with impending intubation
• Anaphylaxis (after epinephrine administration, when intubation is necessary)
• Pediatric emergencies

Important: In patients who are already maximally sympathoadrenally compensated (catecholamine-depleted shock states), the direct myocardial depressant effect of ketamine may predominate when endogenous catecholamine reserves are exhausted. In such situations, a cautious dose reduction to 0.5–1 mg/kg is advisable, ideally with vasopressor support.

Procedural Sedation

For painful procedures in the emergency department (reductions, wound management, cardioversion), ketamine provides well-controllable sedation with analgesia.

• Dosing IV: 1–1.5 mg/kg as an initial bolus
• Repeat dosing: 0.5 mg/kg every 5–10 minutes as needed
• Dosing IM (especially pediatrics): 3–5 mg/kg

Procedural sedation with ketamine requires standardized monitoring: pulse oximetry, capnography, blood pressure measurement, and continuous clinical observation. Airway management equipment must be readily available.

Bronchospasm and Status Asthmaticus

Ketamine is an important escalation option in treatment-refractory bronchospasm. The bronchodilatory effect is based on both direct relaxation of bronchial smooth muscle and sympathomimetically mediated catecholamine release.

• Dosing IV: 0.5–1 mg/kg as a bolus, followed by
• Maintenance infusion: 0.5–1 mg/kg/h
• For intubation in status asthmaticus: 1–2 mg/kg for induction (see above)

Ketamine can also be used as an adjunctive sedative in mechanically ventilated patients with persistent bronchospasm.

Analgosedation During Emergency Mechanical Ventilation

After intubation, ketamine is frequently used for maintenance of sedation, particularly in hemodynamically unstable patients.

• Maintenance dose: 0.5–2 mg/kg/h as a continuous infusion
• Combination: Often with a benzodiazepine (e.g., midazolam 0.03–0.05 mg/kg/h) to reduce psychomimetic side effects

Pediatric Considerations

Ketamine is particularly valuable in pediatric emergency medicine. The intramuscular administration option allows effective sedation and analgesia without IV access – a significant advantage in children in extreme situations.

• Procedural sedation IV: 1–2 mg/kg
• Procedural sedation IM: 3–5 mg/kg
• Analgesia IN: 0.5–1 mg/kg

The incidence of emergence phenomena is significantly lower in children under 10 years compared to adults.

Contraindications and Precautions

Absolute Contraindications

In emergency medicine, there are very few truly absolute contraindications. The principle applies: potential lifesaving benefit outweighs relative risks.

• True allergy to ketamine (extremely rare)
• Situations where an increase in intracranial pressure would be life-threatening – although this classic contraindication is increasingly being questioned (see below)

Relative Contraindications and Precautions

• Traumatic brain injury / elevated intracranial pressure: The absolute contraindication for elevated ICP that was taught for decades is no longer supported by current evidence. Multiple studies show that ketamine, with adequate ventilation, does not cause clinically significant ICP elevation and may even possess neuroprotective properties. In TBI patients who are hemodynamically unstable, ketamine may even be advantageous because it maintains cerebral perfusion pressure through blood pressure stabilization.
• Severe arterial hypertension: Sympathomimetic effect can further increase blood pressure
• Unstable angina / acute coronary syndrome: Heart rate and blood pressure increases raise myocardial oxygen consumption
• Aortic aneurysm / aortic dissection: Blood pressure increase potentially dangerous
• Eclampsia / severe preeclampsia: Relative contraindication due to hypertensive effect
• Psychiatric comorbidities (psychosis, schizophrenia): Increased risk of severe psychomimetic reactions
• Penetrating eye injuries: Ketamine can transiently increase intraocular pressure (clinical relevance debated)

Management of Side Effects

Psychomimetic Side Effects and Emergence Reactions

These are the most feared side effects and the most common reason why ketamine is not used – although they are generally well manageable.

Clinical presentation:

• Vivid dreams, hallucinations
• Dysphoria, anxiety, agitation
• Disorientation, confusion
• Occurring in up to 10–30% of adults, significantly less common in children

Prevention:

• Slow injection (>60 seconds for IV bolus)
• Quiet environment, minimal stimulation during the emergence phase
• Prophylactic administration of midazolam 0.03 mg/kg IV – the evidence is not conclusive, but it is widely practiced
• Low-dose propofol (0.5 mg/kg) as an alternative to benzodiazepines

Treatment of established reactions:

• Midazolam 1–2 mg IV, repeat as needed
• Propofol 0.5–1 mg/kg IV for severe agitation
• Verbal reassurance, low-stimulation environment

Hypersalivation

Ketamine significantly stimulates saliva production. This can be particularly problematic during airway management.

Prevention and treatment:

• Atropine 0.01 mg/kg IV (max. 0.5 mg) or
• Glycopyrrolate 0.005 mg/kg IV
• Suction equipment at the ready

Nausea and Vomiting (PONV)

The incidence of nausea and vomiting after ketamine is approximately 5–15%, particularly with higher doses and in non-fasting patients.

Treatment:

• Ondansetron 0.1 mg/kg IV (max. 4 mg)
• If aspiration risk present: lateral positioning, suction equipment at the ready

Cardiovascular Effects

Sympathomimetic stimulation typically leads to:

• Heart rate increase of 10–25%
• Blood pressure increase of 10–25%
• These effects are desired in most emergency scenarios

In patients where a blood pressure increase is undesirable, combination with low-dose propofol or a benzodiazepine can attenuate the hemodynamic response.

Laryngospasm

Laryngospasm is a rare (incidence <1%) but potentially life-threatening complication, particularly described in children.

Management:

• Immediate positive pressure ventilation (jaw thrust, bag-mask ventilation)
• If unresponsive: succinylcholine 0.5–1 mg/kg IV or 4 mg/kg IM
• Alternatively: rocuronium 1.2 mg/kg IV
• Intubation readiness

Practical Tips for Clinical Use

Quick Reference Dosing Table (Racemic Mixture)

Indication	Route	Dose	Special considerations
Analgesia	IV	0.1–0.3 mg/kg	Slowly over 60 s
Analgesia	IN	0.5–1 mg/kg	Use MAD atomizer
Analgesia	IM	0.5–1 mg/kg	When no IV access available
RSI / Anesthesia induction	IV	1–2 mg/kg	+ Neuromuscular blocking agent
RSI / Anesthesia induction	IM	4–6 mg/kg	Only if no IV access
Procedural sedation	IV	1–1.5 mg/kg	Repeat dosing 0.5 mg/kg
Procedural sedation	IM	3–5 mg/kg	Especially pediatrics
Bronchospasm	IV	0.5–1 mg/kg bolus	Then 0.5–1 mg/kg/h
Maintenance sedation	IV	0.5–2 mg/kg/h	Continuous infusion

Preparation and Practical Notes

• Ketamine is typically available as a 50 mg/ml (= 5%) solution – for analgesic use, dilution to 10 mg/ml (= 1%) is recommended for better titrability
• S-ketamine is usually available as 5 mg/ml (0.5%) or 25 mg/ml (2.5%) – halve the dose!
• For intranasal administration, a highly concentrated solution is advantageous (max. 1 ml per nostril), ideally using a Mucosal Atomization Device (MAD)
• Ketamine is compatible with most common infusion solutions (0.9% NaCl, Ringer's lactate, 5% dextrose)

Common Clinical Errors

• Too-rapid IV injection: Most common cause of dysphoria and psychomimetic reactions at analgesic dosing
• Confusion between racemic mixture and S-ketamine: Double overdosing if not accounted for – always check the label
• Underdosing during RSI: 1 mg/kg may lead to inadequate anesthesia in young, healthy patients – when in doubt, use 2 mg/kg
• Lack of monitoring standards: Pulse oximetry, capnography, and blood pressure measurement are mandatory even with ketamine
• Forgetting aspiration risk: Despite largely preserved protective reflexes, aspiration is possible during deep sedation – keep suction ready

Ketamine in the Context of Advanced Resuscitation

Although ketamine is not a standard medication in the ACLS algorithm, there are relevant points of intersection:

• Post-ROSC phase: In hemodynamically unstable patients after return of spontaneous circulation, ketamine can be a sensible choice for analgosedation and anesthesia induction for intubation
• Peri-arrest situations: In severe bronchospasm as a reversible cause of cardiac arrest (hypoxia), ketamine can be used as adjunctive therapy
• Agitated patients: Severe agitation can make adequate patient care impossible – ketamine IM allows rapid and safe chemical immobilization before a structured evaluation becomes possible

Practical Training

The safe use of ketamine – from subdissociative analgesic dosing to anesthesia induction in shock – requires more than theoretical knowledge. Appropriate dose selection, recognition and management of side effects, and integration into complex emergency algorithms are best trained in realistic simulation scenarios. In the ACLS courses offered by Simulation Tirol, you practice these decisions in hands-on scenarios, including airway management, medication administration, and post-ROSC care – structured according to current AHA guidelines and under the guidance of experienced emergency medicine physicians.

---