Evidence map›Paper›PMID 27500978›Full record

ArticleEpilepsia2016

Midazolam-ketamine dual therapy stops cholinergic status epilepticus and reduces Morris water maze deficits.

Jerome Niquet, Roger Baldwin, Keith Norman, Lucie Suchomelova, Lucille Lumley, Claude G Wasterlain

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epilepsia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05779657 (Efficacy of Combined Ketamine and Midazolam for Treatment of Generalized Convulsive Status Epilepticus in Children .), which is not on this map. Cited by 44 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 2 pooled it
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05779657 phase2 / phase3completednot on this mapstarted 2023, after this paper: background citation

Efficacy of Combined Ketamine and Midazolam for Treatment of Generalized Convulsive Status Epilepticus in Children .

TypeinterventionalSponsorSohag UniversityRan2023 to 2024Enrolled144ConditionsGeneralized Convulsive Status EpilepticusArmsKetamine, Midazolam, Placebo
3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 70 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Review
  6. Review
  7. Pathophysiology of Status Epilepticus Revisited.International journal of molecular sciences · 2025
    Review
  8. Review
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  17. Article
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  19. Review
  20. Why ketamine.Epilepsy & behavior : E&B · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Jerome NiquetDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A.
Roger BaldwinEpilepsy Research Laboratory (151), Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, U.S.A.
Keith NormanEpilepsy Research Laboratory (151), Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, U.S.A.
Lucie SuchomelovaEpilepsy Research Laboratory (151), Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, U.S.A.
Lucille LumleyUS Army Medical Research Institute of Chemical Defense (USAMRICD), Aberdeen Proving Ground, Maryland, U.S.A.
Claude G WasterlainDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A.
VA Greater Los Angeles Healthcare System · USUniversity of California, Los Angeles · USDEVCOM Army Research Laboratory · US

Funding

Rational polytherapy in the treatment of cholinergic seizuresU01NS074926 · NINDS · BRENTWOOD BIOMEDICAL RESEARCH INSTITUTE · PI WASTERLAIN, CLAUDE G · 2011 to 2015
$3.3M
Treatment of Status Epilepticus: A Translational ProposalI01BX000273 · VA · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · PI WASTERLAIN, CLAUDE G · 2009 to 2017
–
BLRD VA I01 BX000273NINDS NIH HHS U01 NS074926
6 · The paper itself

Abstract

objectivePharmacoresistance remains an unsolved therapeutic challenge in status epilepticus (SE) and in cholinergic SE induced by nerve agent intoxication. SE triggers a rapid internalization of synaptic γ-aminobutyric acid A (GABAA ) receptors and externalization of N-methyl-d-aspartate (NMDA) receptors that may explain the loss of potency of standard antiepileptic drugs (AEDs). We hypothesized that a drug combination aimed at correcting the consequences of receptor trafficking would reduce SE severity and its long-term consequences.

methodsA severe model of SE was induced in adult Sprague-Dawley rats with a high dose of lithium and pilocarpine. The GABAA receptor agonist midazolam, the NMDA receptor antagonist ketamine, and/or the AED valproate were injected 40 min after SE onset in combination or as monotherapy. Measures of SE severity were the primary outcome. Secondary outcomes were acute neuronal injury, spontaneous recurrent seizures (SRS), and Morris water maze (MWM) deficits.

resultsMidazolam-ketamine dual therapy was more efficient than double-dose midazolam or ketamine monotherapy or than valproate-midazolam or valproate-ketamine dual therapy in reducing several parameters of SE severity, suggesting a synergistic mechanism. In addition, midazolam-ketamine dual therapy reduced SE-induced acute neuronal injury, epileptogenesis, and MWM deficits. SIGNIFICANCE: This study showed that a treatment aimed at correcting maladaptive GABAA receptor and NMDA receptor trafficking can stop SE and reduce its long-term consequences. Early midazolam-ketamine dual therapy may be superior to monotherapy in the treatment of benzodiazepine-refractory SE.

Indexed as

Status EpilepticusAnimalsAnticonvulsantsBrainCholinergic AgentsDisease Models, AnimalDrug SynergismDrug Therapy, CombinationKetamineLearning DisabilitiesLithium ChlorideMaleMaze LearningMidazolamN-MethylscopolaminePilocarpineAnticonvulsantsCholinergic AgentsKetamineLithium ChlorideMidazolamN-MethylscopolaminePilocarpineValproic AcidCholinergic seizuresEpileptogenesisHippocampal sclerosisNeuronal injuryRefractory status epilepticusSpatial memory

Identifiers

PMID27500978
PMCPMC5012923
OpenAlexW2507902224

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.