The Critical Vector · Flight Deck

Prehospital Ketamine After Midazolam in Status Epilepticus

R. E. Suscitate & A. Systole

One Florida EMS system added ketamine for seizures that kept going after midazolam. More patients arrived at the ED no longer convulsing. The evidence is retrospective, and the question it answers is narrower than the headline.

VERIFIEDZitek et al., Ann Emerg Med 2025Retrospective · before/after

First line

Benzodiazepine at full dose. Prehospital benchmark: IM midazolam 10 mg stopped seizures before ED arrival in 73.4% (RAMPART).

Benzo-resistant, prehospitalTHIS STUDY

Ketamine after midazolam, in place of a second-line antiseizure drug that most ambulances don't carry.

Second line (ED)

Levetiracetam, fosphenytoin, or valproate; each stopped seizures in about half of patients in ESETT.

Refractory

Anesthetic infusions, where ketamine already has a role.

Different question from ket-mid-pediatric-status-epilepticus, which tested ketamine plus midazolam as the first dose in a pediatric RCT.

The study

Element	Detail
Design	Retrospective cohort, before and after a protocol change
Setting	One EMS system in Florida, August 2015 to August 2024
Comparison	New protocol (ketamine after midazolam for continued convulsions) vs the prior protocol (midazolam alone)
Primary outcome	Convulsions stopped before ED arrival, as documented by paramedics

The numbers

94.4%

Convulsions stopped before ED arrival, midazolam then ketamine (matched)

82%

Midazolam alone (matched)

+12.4%

Absolute difference (95% CI 3.1% to 21.7%)

The study found no clear increase in cardiac arrest or intubation with ketamine, and intravenous or intraosseous ketamine had the highest termination rates. A companion case series from the same region reported ketamine stopped midazolam-resistant convulsions in 56 of 57 adults.

Why caution

Before/after, not randomized. Anything else that changed in that system over nine years is mixed into the result.
Paramedic-documented cessation. Ketamine stops visible convulsions; nonconvulsive status can continue underneath.
Benzodiazepine underdosing was common, which inflates the apparent benefit of anything given next.
No comparison to a real second-line drug (levetiracetam, fosphenytoin, valproate).
One system, no long-term neurologic outcomes.

At the bedside

Dose the benzodiazepine fully first. Most "benzo failures" are underdosed benzodiazepines.

Then ketamine is a reasonable prehospital rescue when convulsions continue and a second-line antiseizure drug isn't available or would be delayed. On arrival, start a standard second-line agent and consider EEG if the patient doesn't wake.

Sources

Zitek T, Scheppke KA, Antevy P, et al. Midazolam and ketamine for convulsive status epilepticus in the out-of-hospital setting. Ann Emerg Med. 2025;85(4):305-312.
Scheppke KA, Pepe PE, et al. Effectiveness of ketamine as a rescue drug for patients experiencing benzodiazepine-resistant status epilepticus in the prehospital setting. 2024. (PMC11627481)
Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus (RAMPART). N Engl J Med. 2012;366(7):591-600.
Kapur J, Elm J, Chamberlain JM, et al. Randomized trial of three anticonvulsant medications for status epilepticus (ESETT). N Engl J Med. 2019;381(22):2103-2113.