At what doses does ketamine result in dissociative/anesthetic effects? what dose range is recommended for non-intubated ketamine infusion in status epilepticus patients?

Comment by InpharmD Researcher

Ketamine produces dose-dependent dissociative and anesthetic effects, with intravenous doses of 1–4.5 mg/kg (average approximately 2 mg/kg) commonly used for anesthetic induction and procedural sedation, while lower subanesthetic doses such as 0.3–0.5 mg/kg IV boluses and infusions of 0.1–0.2 mg/kg/hour are generally used for analgesia. No guideline or consensus recommendation specifically defines a ketamine infusion dose range for non-intubated patients with status epilepticus. Available evidence consists primarily of case series and observational studies in which dosing varied considerably, with reported infusion rates ranging from 0.1 to 4 mg/kg/hour in non-intubated patients and lower infusion rates of approximately 0.6–1.8 mg/kg/hour being most commonly used (Tables 1-4). The literature supports substantial variability in dosing and does not establish a definitive infusion range for non-intubated status epilepticus patients.

Background

The American Society of Regional Anesthesia and Pain Medicine, American Academy of Pain Medicine, and American Society of Anesthesiologists consensus guidelines describe ketamine as a dissociative anesthetic with dose-dependent clinical use spanning analgesic, subanesthetic, and procedural sedation/anesthetic ranges: the FDA-listed anesthetic induction dose is 1–4.5 mg/kg IV, with an average dose of 2 mg/kg, and common subanesthetic analgesic dosing in clinical practice is an IV bolus of 0.3–0.5 mg/kg, with or without an infusion usually initiated at 0.1–0.2 mg/kg/hour; for acute pain settings without intensive monitoring, the consensus recommendation is that bolus doses generally not exceed 0.35 mg/kg and infusions generally not exceed 1 mg/kg/hour, while noting that lower infusion doses of 0.1–0.5 mg/kg/hour may be needed to balance analgesia and adverse effects. The Royal Children’s Hospital Melbourne clinical practice guideline characterizes the ketamine dissociative state as a trance-like state with catalepsy, effective analgesia, usually total amnesia, maintained airway reflexes, slight increases in blood pressure and heart rate, and typical nystagmus and lacrimation, and recommends procedural sedation dosing of 1–1.5 mg/kg IV over 1–2 minutes with 0.25–0.5 mg/kg incremental IV doses every 10 minutes as needed, up to a maximum of 4.5 mg/kg, while stating that IV doses greater than 2.5 mg/kg are associated with increased adverse-event risk; it also lists IM procedural sedation dosing as 4 mg/kg initially, up to a maximum of 6 mg/kg, with a repeat 2 mg/kg dose after 10 minutes if sedation is inadequate. Neither source provides a ketamine infusion dose range specifically for non-intubated patients with status epilepticus, and the Royal Children’s Hospital Melbourne guideline explicitly states that uses other than procedural sedation are beyond its scope; therefore, based only on these attached sources, the only directly stated non-intensively monitored infusion recommendation is the American Society of Regional Anesthesia and Pain Medicine, American Academy of Pain Medicine, and American Society of Anesthesiologists consensus guideline range of generally not exceeding 1 mg/kg/hour, with 0.1–0.5 mg/kg/hour described as a lower-dose range used to balance analgesia and adverse effects, but this is not a status epilepticus recommendation. [1], [2]

A 2018 systematic review described ketamine as having a pharmacological profile characterized by a “dissociative anesthetic state,” defined as anesthesia with catalepsy, catatonia, analgesia, and amnesia that does not necessarily cause loss of consciousness; however, the review did not identify a specific ketamine dose threshold at which dissociative or anesthetic effects occur. Across published refractory status epilepticus studies, ketamine dosing was highly heterogeneous and did not appear to be an independent prognostic factor. In the adult case series, reported ketamine doses ranged from 0.07 to 15 mg/kg/h, while in paediatric case series and reported doses ranged from 0.04 to 10 mg/kg/h. The review did not provide a recommended dose range for non-intubated ketamine infusion in status epilepticus patients. It reported that endotracheal intubation was avoided or unnecessary in selected cases, including two adult patients in whom ketamine was effective, five children with non-convulsive status epilepticus treated with oral ketamine, and five of 13 children with refractory convulsive status epilepticus in the Ilvento et al. series, where the mean ketamine infusion dose was 1.8 mg/kg/h with a reported range of 0.42–3.6 mg/kg/h. [3]

A 2018 systematic review and case report series evaluated ketamine use in refractory status epilepticus (RSE) and found that, although ketamine is described as standard in anesthetic induction, the paper does not specify the dose at which ketamine produces dissociative or anesthetic effects and does not provide a recommended dose range for non-intubated ketamine infusion in status epilepticus patients. Across the reviewed RSE literature, ketamine dosing varied substantially: adult studies reported bolus doses of 0.5–5 mg/kg and maintenance infusion doses of 0.05–10.5 mg/kg/hour, while pediatric studies reported bolus doses of 0.002–5 mg/kg and continuous infusion doses of 0.0075–10.5 mg/kg/hour. The authors emphasized that no definitive ketamine protocol exists for RSE, that there is scarce safety information for long-term infusion, and that prolonged high-dose ketamine, particularly with midazolam, was associated in their review and cases with metabolic acidosis and hemodynamic instability. Therefore, available evidence supports reporting observed RSE dosing ranges rather than defining a dissociative/anesthetic threshold or recommending a non-intubated infusion range. [4]

References: [1] Schwenk ES, Viscusi ER, Buvanendran A, et al. 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. Reg Anesth Pain Med. 2018;43(5):456-466. doi:10.1097/AAP.0000000000000806
[2] The Royal Children’s Hospital Melbourne. Clinical Practice Guidelines: Ketamine Use for Procedural Sedation. Updated December 2021. Accessed June 19, 2026.
[3] Rosati A, De Masi S, Guerrini R. Ketamine for Refractory Status Epilepticus: A Systematic Review. CNS Drugs. 2018;32(11):997-1009. doi:10.1007/s40263-018-0569-6
[4] Golub D, Yanai A, Darzi K, Papadopoulos J, Kaufman B. Potential consequences of high-dose infusion of ketamine for refractory status epilepticus: case reports and systematic literature review. Anaesth Intensive Care. 2018;46(5):516-528.
Relevant Prescribing Information

INDICATIONS [5]
Ketamine hydrochloride injection is indicated:
As the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation.
For the induction of anesthesia prior to the administration of other general anesthetic agents.
As a supplement to other anesthetic agents.

DOSAGE AND ADMINISTRATION [5]
Recommended Dosage and Administration
Induction of Anesthesia
Intravenous Route: The initial dose of ketamine hydrochloride injection administered intravenously may range from 1 mg/kg to 4.5 mg/kg. The average amount required to produce 5 minutes to 10 minutes of surgical anesthesia within 30 seconds following injection is 2 mg/kg.

Pharmacodynamics [5]
Nervous System
Ketamine is a rapidly-acting general anesthetic producing a dissociative anesthetic state characterized by profound analgesia, normal pharyngeal-laryngeal reflexes, normal or slightly enhanced skeletal muscle tone, cardiovascular and respiratory stimulation, and occasionally a transient and minimal respiratory depression

References: [5] Ketamine hydrochloride (injection). Prescribing information. Baxter Healthcare Corporation.; 2025.
Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

At what doses does ketamine result in dissociative/anesthetic effects? what dose range is recommended for non-intubated ketamine infusion in status epilepticus patients?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-4 for your response.


Safety and Efficacy of Ketamine Without Intubation in the Management of Refractory Seizures: A Case Series
Design

Retrospective cohort study

N= 28

Objective To describe the safety and efficacy of ketamine infusions in patients with refractory seizure without intubation
Study Groups All patients (n= 28)
Inclusion Criteria Adult patients who were not intubated at the time of initiation of a ketamine infusion for refractory seizures
Exclusion Criteria Care deemed futile prior to initiation of the ketamine infusion, especially patients with anoxic brain injury or hospice patients
Methods Retrospective review of adult patients admitted to the neurocritical care unit at Methodist University Hospital. Ketamine infusion was administered as the first continuous infusion anesthetics (CIA) for refractory seizures without intubation. Responders were defined as patients with resolution of seizures within 24 hours of initiation without the need for intubation or additional CIAs. 
Duration November 1, 2018, to December 31, 2022
Outcome Measures Response to ketamine (resolution of seizures within 24 hours without intubation or additional CIAs), hemodynamic safety
Baseline Characteristics   All patients (n= 28)
Female 18 (64.3%)
Age, years 62 
African American 23 (82.1%)

Past medical history

Hypertension

Heart failure

Coronary artery disease

End-stage renal disease

Epilepsy

 

22 (78.6%)

4 (14.3%)

4 (14.3%)

1 (3.6%)

15 (53.6%)

Structural seizure etiology 23 (82.1%)

Baseline hemodynamics

Systolic blood pressure, mmHg

Diastolic blood pressure, mmHg

Heart rate, beats per minute

Respiratory rate, breaths per minute

 

134 ± 20.8

76.5 ± 21.3

86 ± 21.3

18 ± 2.3

Results   All patients (n= 28)
Responders 20 (71.4%)
Non-responders 8 (28.6%)
Required intubation & additional CIA 6
Hypotension (SBP < 90 mmHg) 31.8%
Hypertension (SBP > 180 mmHg) 39.3%
Most patients (78.6%) received an initial bolus of approximately 0.9 mg/kg, followed by a continuous infusion initiated at 10 mcg/kg/min in 89.3% of patients. Maximum infusion rates ranged from 10 to 30 mcg/kg/min, with 10 mcg/kg/min being the most commonly utilized dose. The median infusion duration was 39.8 hours, and seizure resolution without intubation or additional anesthetic therapy was achieved in 71.4% of patients. No adverse events required ketamine dose reduction or discontinuation.
Adverse Events See Results
Study Author Conclusions Ketamine represents a safe and effective treatment option for refractory seizures and has potential to reduce morbidity associated with intubation in a carefully selected patient population. Early initiation may increase the likelihood of success
Critique The study provides valuable insights into the use of ketamine for refractory seizures without intubation, highlighting its potential to reduce morbidity. However, the single-center, retrospective design and small sample size limit the generalizability of the findings. The lack of a comparison group and the observational nature of the study also pose limitations in establishing causality
References:
[1] [1] Kimmons LA, Alzayadneh M, Metter EJ, Alsherbini K. Safety and Efficacy of Ketamine Without Intubation in the Management of Refractory Seizures: A Case Series. Neurocrit Care. 2024;40(2):689-697. doi:10.1007/s12028-023-01811-4

Ketamine to Prevent Endotracheal Intubation in Adults with Refractory Non-convulsive Status Epilepticus: A Case Series
Design

Case series

N= 9

Objective To describe the experience with the early use of intravenous ketamine as the first anesthetic agent in patients with refractory non-convulsive status epilepticus (NCSE) to avoid endotracheal intubation
Study Groups

Patients avoiding endotracheal intubation (n= 5)

Patients requiring endotracheal intubation (n= 4)

Inclusion Criteria Adult patients (age 18 and older) admitted between June 2020 to January 2023 with the diagnosis of SE, confirmed by EEG, in whom ketamine was used as the first anesthetic agent
Exclusion Criteria Not explicitly stated
Methods Retrospective chart review of patients with refractory NCSE managed in the Neurointensive Care Unit at a university-affiliated tertiary care hospital. Ketamine was used as the first anesthetic agent. 
Duration June 2020 to January 2023
Outcome Measures Avoidance of endotracheal intubation while on ketamine infusion, cessation of both clinical and electrographic seizures within 24 hours of ketamine administration
Baseline Characteristics   Patients avoiding endotracheal intubation (n= 5) Patients requiring endotracheal intubation (n= 4)
Median age, years  61 (26–72) 65 (45–70)
Female 2 0

Race

Black/African American

White

 

4

1

 

3

1

Mean Glasgow Coma Scale (GCS) on admission 10.7 ± 3.59 8.7 ± 4.3

Seizure etiology

Structural

Non-structural

 

3

2

 

2

2

History of epilepsy 4 3
Mean number of ASMs given prior to ketamine infusion 3 ± 0 3.25 ± 1.26
Total median dose of Benzodiazepines prior to Ketamine, mg/kg  0.16 (0.09–0.18) 0.13 (0.12–0.4)
Mean duration between seizure onset to start of ketamine infusion, h 32.4 ± 21.5 30 ± 21.7
Mean duration of ketamine infusion, h 62.42 ± 34.14 57.8 ± 39.5
Median maximum dose of ketamine, mg/kg/h 2 (1–4) 2 (0.5–4)
Number of patients with successful cessation of seizures with ketamine 5 1
Mean number of days on the ventilator 0 18.12 ± 22.5
Mean length of stay in the neurocritical care unit 13.2 ± 7.50 31.25 ± 16.62
Results   Patients avoiding endotracheal intubation (n= 5) Patients requiring endotracheal intubation (n= 4)
Avoidance of intubation 5 0
Successful cessation of seizures with ketamine 5 1
Development of pneumonia 3 1
In-hospital mortality 0 2
Adverse Events Hypersalivation and pneumonia were the most common ketamine associated adverse events. One patient developed agitation and another experienced hypotension requiring vasopressor support.
Study Author Conclusions The use of ketamine as the primary anesthetic agent may be a reasonable option to avoid endotracheal intubation in a subset of patients with refractory NCSE
Critique The study is limited by its small sample size, retrospective design, and reliance on information obtained from chart review. The lack of a comparison group and potential selection bias due to the discretion of the treating physician in administering ketamine may affect the generalizability of the findings. Future prospective studies are needed to validate these findings
References:
[1] [1] Syed MJ, Zutshi D, Muzammil SM, Mohamed W. Ketamine to Prevent Endotracheal Intubation in Adults with Refractory Non-convulsive Status Epilepticus: A Case Series. Neurocrit Care. 2024;40(3):976-983. doi:10.1007/s12028-023-01853-8

Ketamine Therapy for Non-Intubated Adults with Status Epilepticus: A Case Series
Design

Case series study

N= 4

Objective To examine the effectiveness and tolerability of ketamine as an intubation-sparing therapy for non-intubated patients with status epilepticus
Study Groups All patients (n= 4)
Inclusion Criteria Non-intubated patients with status epilepticus treated with ketamine at two Boston area academic medical centers
Exclusion Criteria Not specified
Methods Four cases were reported where patients received ketamine for SE without requiring intubation. Doses varied: Patient One received two 3 mg/kg doses; Patient Two received three 0.5 mg/kg doses followed by a 10 mcg/kg/min infusion; Patient Three started at 2 mcg/kg/min, up-titrated to 3 mcg/kg/min; Patient Four started at 5 mcg/kg/min, up-titrated to 20 mcg/kg/min. Vitals and EEG monitoring were used to assess response. 
Duration Not specified
Outcome Measures Termination of status epilepticus 
Baseline Characteristics   All patients (n= 4)
Age, years 22, 73, 66, 59
Gender 3 Male, 1 Female
Seizure Type Refractory status epilepticus, focal status epilepticus, focal status epilepticus due to CNS lymphoma, focal status epilepticus
Results   Response to Ketamine Hemodynamic Changes
Patient One Improvement in electrographic seizure activity Hypertension, tachycardia, oxygen saturation decline
Patient Two Seizures less frequent and lower amplitude No significant changes
Patient Three Improved verbal output and alertness No hemodynamic alterations
Patient Four Partial treatment response No significant changes
Adverse Events Patient One experienced hypertension, tachycardia, and a decline in oxygen saturation. Other patients did not experience significant hemodynamic changes
Study Author Conclusions Low-dose ketamine appears to be effective in terminating established SE and was well-tolerated in non-intubated patients
Critique The study provides valuable insights into the use of ketamine for SE in non-intubated patients, highlighting its potential as an intubation-sparing therapy. However, the small sample size and case series design limit the generalizability of the findings. Because the findings are available only as a poster abstract, key methodological and clinical details may be missing, which introduces some uncertainty.
References:
[1] MacDonald B, Macdonald B, Webb A, Piotrowski K, Ack S, Rosenthal E. Ketamine therapy for non-intubated adults with status epilepticus: a case series. Presented at: American Epilepsy Society Annual Meeting; December 4, 2023. Abstract 3.298. Accessed June 19, 2026.

Ketamine to treat super-refractory status epilepticus
Design

Retrospective, single-center study

N= 68

Objective To test ketamine infusion efficacy in the treatment of super-refractory status epilepticus (SRSE) and to study the effect of high doses of ketamine on brain physiology as reflected by invasive multimodality monitoring (MMM)
Study Groups All patients (n= 68)
Inclusion Criteria Adult patients (>18 years old) with SRSE admitted to the neurologic intensive care unit at Columbia University Medical Center between January 1, 2009, and December 31, 2018
Exclusion Criteria Not specified
Methods A consecutive series of 68 patients with SRSE were treated with ketamine and monitored with scalp EEG. Eleven patients underwent MMM at the time of ketamine administration. The average dose of ketamine infusion was 2.2 ± 1.8 mg/kg/h, with a median duration of 2 (1–4) days. Midazolam was used concurrently, started at a median of 0.4 (0.1–1.0) days before ketamine.
Duration January 1, 2009, to December 31, 2018
Outcome Measures Seizure control within 24 hours of ketamine initiation (complete cessation or >50% reduction of seizure burden)
Baseline Characteristics   Patients with SRSE (n = 68)
Age, years 53 ± 19
Female 46 (68%)
Baseline modified Rankin Scale (mRS) 0 ± 1
Baseline extended Glasgow Outcome Scale (GOSE) 8 ± 2

Admission diagnosis

Cardiac arrest

New-onset refractory status epilepticus (NORSE)

Ischemia/ICH/SAH

Infection

Epilepsy

Other

 

18 (27%)

12 (18%)

11 (16%)

8 (12%)

6 (9%)

13 (19%)

Status epilepticus severity score (STESS) 4 ± 1
Focal seizures on EEG 39 (57%)
In-hospital mortality 31 (46%)
Results   Patients with SRSE (n = 68)
Seizure burden decreased by at least 50% within 24 hours 55 (81%)
Complete seizure cessation within 24 hours 43 (63%)
Seizure burden decreased by at least 50% after stopping ketamine 54 (79%)
Complete seizure cessation after stopping ketamine 44 (65%)
Adverse Events Not specified
Study Author Conclusions Ketamine treatment was associated with a decrease in seizure burden in patients with SRSE. High-dose ketamine infusions are associated with decreased vasopressor requirements without increased intracranial pressure.
Critique The study is limited by its retrospective, single-center design, which may introduce subject heterogeneity and limit generalizability. The response to ketamine could be influenced by coadministration of other drugs or spontaneous improvement. The study did not compare patients who received ketamine with those who did not, and ketamine was started at the discretion of the treating physician, potentially introducing selection bias. Further prospective studies are needed to evaluate ketamine's efficacy in SRSE treatment.
References:
[1] [1] Alkhachroum A, Der-Nigoghossian CA, Mathews E, et al. Ketamine to treat super-refractory status epilepticus. Neurology. 2020;95(16):e2286-e2294. doi:10.1212/WNL.0000000000010611