Clinical Scenario
A 45-year-old patient with refractory convulsive status epilepticus (RSE) is unresponsive to benzodiazepines and a second-line antiseizure medication. The ICU team considers ketamine as an adjunct therapy.
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ACEP Now: June 2026 (Digital)When/Why Would You Use This Drug?
Ketamine is considered in refractory SE (failure of benzodiazepines and at least one additional antiseizure drug) and super-refractory SE (SRSE) (ongoing seizures despite more than 24 hours of treatment, including anesthetics). Recent evidence suggests that ketamine may also be effective in early SE or prehospital benzodiazepine-resistant SE. It provides seizure control when GABAergic therapies fail.
How Does This Drug Work?
Ketamine is an NMDA receptor antagonist that prevents excitotoxic neuronal damage and blocks glutamate-mediated seizure propagation. In prolonged SE, GABA_A receptor internalization reduces benzodiazepine efficacy, whereas NMDA receptors are upregulated, making ketamine a rational treatment choice.
Bedside Tips
- Dosing: 0.5–1 mg/kg IV bolus, followed by 1–5 mg/kg/hr infusion. Higher doses (up to 10 mg/kg/hr) have been used in SRSE. Can be used in combination with midazolam or propofol for a synergistic effect.
- Prehospital Use: 100 mg IV/IM/IN/IO (or 1 mg/kg IM/IN in children) has been effective for in the prehospital setting.
- Hemodynamics: Unlike propofol or barbiturates, ketamine supports blood pressure and may reduce vasopressor requirements.
- Monitoring: Continuous EEG monitoring is recommended.
- Tapering: Gradually wean to prevent seizure recurrence.
Summary of Key Studies on Ketamine for Status Epilepticus
| Study | Design & Sample Size | Population | Intervention | Outcomes |
|---|---|---|---|---|
| Scheppke et al., 2024 | Observational; 81 patients | Prehospital, benzodiazepine-resistant SE in adults and children | Ketamine IV/IM/IN/IO after midazolam failure | – Seizure termination: 98.2 percent in adults, 73 percent in children. 100 percent success in nine cases where ketamine was first-line. – No intubations or major adverse effects. – Supports prehospital use as an effective second-line agent. |
| Rosati et al., 2018 | Systematic review; 248 patients (12 case series, including 29 children) | Pediatric + adult RSE/SRSE; median age 43.5 yrs (range 2 months–67 yrs) | IV ketamine as third-line therapy, after failed benzodiazepines ± conventional anesthetics | Efficacy time-dependent: 64 percent seizure control when given early (RSE ~3 days) versus 32 percent when delayed (~26 days).- Dose not an independent prognostic factor — wide dose heterogeneity across studies.- Intubation avoided in 12 patients (10 children), including 7 treated with oral ketamine for non-convulsive SE.- Supports earlier use of ketamine in the RSE treatment ladder. |
| Gaspard et al., 2013 | Multicenter retrospective; 60 patients | ICU, refractory SE | Ketamine infusion | – Seizure control: 57 percent success rate. – Earlier use (<7 days) associated with lower mortality (16 percent versus 56 percent). – Higher doses (≥0.9 mg/kg/h) linked to better seizure suppression. – No significant adverse hemodynamic effects. |
| Höfler et al., 2016 | Retrospective; 42 patients | ICU, super-refractory SE | Ketamine infusion | – EEG suppression: 69 percent of cases. – Median dose: 2.5 mg/kg/hr. – Lower rates of hypotension and less vasopressor need versus propofol. |
| Alkhachroum et al., 2020 | Retrospective; 68 patients | ICU, super-refractory SE | Ketamine infusion | – Seizure cessation: 63 percent. – Mean dose: 2.2 mg/kg/hr. – No increase in ICP (safe for neurocritical care patients). – Some patients required fewer vasopressors after ketamine initiation. |
| Srinivas et al., 2023 | Multivariable analysis; 53 patients | ICU, refractory SE | Ketamine infusion | – Improved seizure control when combined with propofol. – Best success rate with doses >3 mg/kg/hr. – Shorter ICU stays versus barbiturate-based coma. |
| Lele et al., 2026 | Systematic review + meta-analysis; 14 studies, 388 adult patients | Adults with RSE/SRSE (249 responders, 139 nonresponders) | IV ketamine infusion; mean maintenance dose 2.5 ± 1.4 mg/kg/hr; mean duration 5.0 days | – Pooled seizure cessation rate: 64 percent (95 percent CI 49–76 percent). – Responders received ketamine earlier than nonresponders (3.2 versus 4.3 days, P < 0.0001). – No significant difference in maintenance dose or infusion duration between responders and nonresponders. – Adverse-event discontinuation rare (0.7 percent, 3 of 55). – Largest pooled ketamine-specific estimate to date; supports early initiation but calls for prospective trials. |
| Ilvento et al., 2015 | Retrospective; 9 pediatric patients | Pediatric refractory SE | Ketamine infusion | – Seizure control in all cases. – No intubation required. – Well tolerated, no major adverse effects. – Suggests potential first-line role in pediatric refractory SE. |
Dr. Pruitt is a clinical pharmacist coordinator and emergency medicine residency program director of pharmacy services at Carolinas Medical Center in Charlotte, NC. He is also president and executive director of the Society of Emergency Medicine Pharmacists.
Dr. Gibbs is the chair of the department of emergency medicine at Carolinas Medical Center in Charlotte, NC.
References
- Scheppke KA, Pepe PE, Garay SA, Coyle CW, Antevy PM, Perlmutter MC, et al. Effectiveness of Ketamine as a Rescue Drug for Patients Experiencing Benzodiazepine-Resistant Status Epilepticus in the Prehospital Setting. Crit Care Explor. 2024;6(12): e1186. https://doi.org/10.1097/CCE.0000000000001186.
- Rosati A, De Masi S, Guerrini R. Ketamine for Refractory Status Epilepticus: A Systematic Review. CNS Drugs. 2018;32(11):997–1009. https://pubmed.ncbi.nlm.nih.gov/30232735. https://doi.org/10.1007/s40263-018-0569-6
- Gaspard N, Foreman B, Judd LM, Brenton JN, Nathan BR, and McCoy BM. Intravenous Ketamine for the Treatment of Refractory and Super-Refractory Status Epilepticus: A Retrospective Multicenter Study.” Epilepsia. 2013;54 (8): 1498-1503. https://pubmed.ncbi.nlm.nih.gov/23861312/.
- Höfler J, Rohracher A, Kalss G, Zimmermann G, Dobesberger J, and Pilz G. (S)-Ketamine in Refractory and Super-Refractory Status Epilepticus: A Retrospective Study. CNS Drugs. 2016; 30(9): 869-876. https://pubmed.ncbi.nlm.nih.gov/27395326/.
- Alkhachroum A, Der-Nigoghossian CA, Mathews E, Massad N, Letchinger R, and Doyle K. Ketamine to Treat Super-Refractory Status Epilepticus. Neurology. 2020; 95(16): e2286-e2294. https://pubmed.ncbi.nlm.nih.gov/32816984/.
- Srinivas M, Parker D, Millis S, Marawar R, Zutshi D, Basha MM . Factors Associated with Refractory Status Epilepticus Termination Following Ketamine Initiation: A Multivariable Analysis Model. Neurocrit Care. 2023;38(2): 235-241. https://pubmed.ncbi.nlm.nih.gov/37242669/.
- Lele AV, Raquer A, Mejia-Mantilla J, Tsan SEH, Shrestha GS, Lin V, et al. Efficacy of IV Ketamine in Refractory/Super-Refractory Status Epilepticus: A Systematic Review and Meta-Analysis. Neurol Clin Pract. 2026;16(2):e200584. https://pubmed.ncbi.nlm.nih.gov/41550426/. https://doi.org/10.1212/CPJ.0000000000200584
- Ilvento L, Rosati A, Marini C, L’Erario M, Mirabile L, Guerrini R. Ketamine in refractory convulsive status epilepticus in children avoids endotracheal intubation. Epilepsy Behav. 2015 Aug;49:343-346. doi: 10.1016/j.yebeh.2015.06.019. Epub 2015 Jul 16. PMID: 26189786.
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