Ketamine in adult super‐refractory status epilepticus: Efficacy analysis on a prospective registry

Caranzano, Leonardo; Nový, Jan; Rossetti, Andrea O.

doi:10.1111/ane.13610

Cited by 18 publications

(25 citation statements)

References 19 publications

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“…49 Other systematic reviews on ketamine examined several clinical studies on RSE and SRSE with very heterogeneous data, highlighting the challenges of drawing valuable conclusions. [50][51][52][53] Fang and Wang concluded that ketamine appears to be effective and relatively safe for the control of multidrug-resistant RSE in children and adults. 51 Hofler and Trinka reported an overall success rate of 74% in adults and 73% in children.…”

Section: Clinical Role Of Ketamine In Se Treatmentmentioning

confidence: 99%

“…57 When considering ketamine dose in the reported studies, the loading dose was 1.5-5 mg/kg, with a maximum infusion rate of 15 mg/kg/h. 41,[51][52][53] In children, the bolus was 2-3 mg/kg and maintenance rate 2-7 mg/kg/h. 54,55 No Cochrane systematic reviews were found on ketamine and SE.…”

Section: Clinical Role Of Ketamine In Se Treatmentmentioning

confidence: 99%

“…Ketamine doses were extremely heterogeneous and did not appear to be an independent prognostic factor 49 . Other systematic reviews on ketamine examined several clinical studies on RSE and SRSE with very heterogeneous data, highlighting the challenges of drawing valuable conclusions 50–53 . Fang and Wang concluded that ketamine appears to be effective and relatively safe for the control of multidrug‐resistant RSE in children and adults 51 .…”

Section: Clinical Role Of Ketamine In Se Treatmentmentioning

confidence: 99%

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Ketamine as advanced second‐line treatment in benzodiazepine‐refractory convulsive status epilepticus in children

et al. 2023

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Status epilepticus (SE) is one of the most common neurological emergencies in children. To date, there is no definitive evidence to guide treatment of SE refractory to benzodiazepines. The main objectives of treatment protocols are to expedite therapeutic decisions and to use fast-and short-acting medications without significant adverse effects. Protocols differ among institutions, and most frequently valproate, phenytoin, and levetiracetam are used as second-line treatment. After failure of first-and second-line medications, admission to the intensive care unit and continuous infusion of anesthetics are usually indicated. Ketamine is a noncompetitive N-methyl-D-aspartate receptor antagonist that has been safely used for the treatment of refractory SE in adults and children. In animal models of SE, ketamine demonstrated antiepileptic and neuroprotective properties and synergistic effects with other antiseizure medications. We reviewed the literature to demonstrate the potential role of ketamine as an advanced second-line agent in the treatment of SE. Pharmacological targets, pathophysiology of SE, and the receptor trafficking hypothesis are reviewed and presented. The pharmacology of ketamine is outlined with related properties, advantages, and side effects. We summarize the most recent and relevant publications on experimental and clinical studies on ketamine in SE. Key expert opinion is also reported. Considering the current knowledge on SE pathophysiology, early sequential polytherapy should include ketamine for its wide range of positive assets. Future research and clinical trials on SE pharmacotherapy should focus on the role of ketamine as second-line medication. K E Y W O R D S ketamine, pediatric, pharmacotherapy, seizures F I G U R E 5 Dual therapy in a model of lithium-pilocarpine-induced convulsive status epilepticus (SE) in rats. The left panels show the compressed electroencephalogram (EEG) from SE control (Cont), midazolam (Mz), ketamine (Ket), or midazolam-ketamine animals up to 75 min following treatment (tr.). The right panels show the magnified 6-s EEG traces prior to SE or following SE (marked by vertical lines a-c). Vertical bar = .5 mV; horizontal bar = 1 s. From Niquet et al. 46 Reproduced with permission provided by John Wiley and Sons and the Copyright Clearance Center.

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Section: Clinical Role Of Ketamine In Se Treatmentmentioning

confidence: 99%

Section: Clinical Role Of Ketamine In Se Treatmentmentioning

confidence: 99%

Section: Clinical Role Of Ketamine In Se Treatmentmentioning

confidence: 99%

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Ketamine as advanced second‐line treatment in benzodiazepine‐refractory convulsive status epilepticus in children

et al. 2023

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“…Its results suggest that ketamine did not affect ICP even at prolonged anesthetic dosages, as do the results of a recent comprehensive analysis on non-traumatic neurological illness [ 89 ], and decreased vasopressor requirement. A 2022 prospective study with 11 patients with SRSE found lesser permanent control of SE (27%) compared to earlier retrospective studies (28–96%) [ 90 ]. Due to patient selection bias, this study may suggest that the efficacy of ketamine is not as good as other studies have demonstrated.…”

Section: Sementioning

confidence: 84%

The Roles of Glutamate Receptors and Their Antagonists in Status Epilepticus, Refractory Status Epilepticus, and Super-Refractory Status Epilepticus

et al. 2023

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Status epilepticus (SE) is a neurological emergency with a high mortality rate. When compared to chronic epilepsy, it is distinguished by the durability of seizures and frequent resistance to benzodiazepine (BZD). The Receptor Trafficking Hypothesis, which suggests that the downregulation of γ-Aminobutyric acid type A (GABAA) receptors, and upregulation of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors play major roles in the establishment of SE is the most widely accepted hypothesis underlying BZD resistance. NMDA and AMPA are ionotropic glutamate receptor families that have important excitatory roles in the central nervous system (CNS). They are both essential in maintaining the normal function of the brain and are involved in a variety of neuropsychiatric diseases, including epilepsy. Based on animal and human studies, antagonists of NMDA and AMPA receptors have a significant impact in ending SE; albeit most of them are not yet approved to be in clinically therapeutic guidelines, due to their psychomimetic adverse effects. Although there is still a dearth of randomized, prospective research, NMDA antagonists such as ketamine, magnesium sulfate, and the AMPA antagonist, perampanel, are regarded to be reasonable optional adjuvant therapies in controlling SE, refractory SE (RSE) or super-refractory SE (SRSE), though there are still a lack of randomized, prospective studies. This review seeks to summarize and update knowledge on the SE development hypothesis, as well as clinical trials using NMDA and AMPA antagonists in animal and human studies of SE investigations.

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“…19 However, in other case series the efficacy of ketamine after weaning varies significantly between 28% and 96% of cases. 20 Intravenous pentobarbital as part of a suppression-burst pattern (SBP) anesthesia for at least 72 h has proven to be effective in terminating SRSE in a small retrospective study of 31 patients with an efficacy of 90% during anesthesia. However, weaning from pentobarbital anesthesia was associated with withdrawal seizures in 50% of patients and the authors reported to have added PB to the AED scheme to allow for successful weaning thereafter.…”

Section: Discussionmentioning

confidence: 99%

Phenobarbital in super‐refractory status epilepticus (PIRATE): A retrospective, multicenter analysis

et al. 2023

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Objective Super‐refractory status epilepticus (SRSE) is an enduring or recurring SE after 24 h or more of general anesthesia. This study aimed to evaluate the efficacy and safety of phenobarbital (PB) for the treatment of SRSE. Methods This retrospective, multicenter study included neurointensive care unit (NICU) patients with SRSE treated with PB between September 2015 and September 2020 from six participating centers of the Initiative of German NeuroIntensive Trial Engagement (IGNITE) to evaluate the efficacy and safety of PB treatment for SRSE. The primary outcome measure was seizure termination. In addition, we evaluated maximum reached serum levels, treatment duration, and clinical complications using a multivariate generalized linear model. Results Ninety‐one patients were included (45.1% female). Seizure termination was achieved in 54 patients (59.3%). Increasing serum levels of PB were associated with successful seizure control (per μg/mL: adjusted odds ratio [adj.OR] = 1.1, 95% confidence interval [CI] 1.0–1.2, p < .01). The median length of treatment in the NICU was 33.7 [23.2–56.6] days across groups. Clinical complications occurred in 89% (n = 81) of patients and included ICU‐acquired infections, hypotension requiring catecholamine therapy, and anaphylactic shock. There was no association between clinical complications and treatment outcome or in‐hospital mortality. The overall average modified Rankin scale (mRS) at discharge from the NICU was 5 ± 1. Six patients (6.6%) reached mRS ≤3, of whom five were successfully treated with PB. In‐hospital mortality was significantly higher in patients in whom seizure control could not be achieved. Significance We observed a high rate in attainment of seizure control in patients treated with PB. Success of treatment correlated with higher dosing and serum levels. However, as one would expect in a cohort of critically ill patients with prolonged NICU treatment, the rate of favorable clinical outcome at discharge from the NICU remained extremely low. Further prospective studies evaluating long‐term clinical outcome of PB treatment as well as an earlier use of PB at higher doses would be of value.

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Ketamine in adult super‐refractory status epilepticus: Efficacy analysis on a prospective registry

Cited by 18 publications

References 19 publications

Ketamine as advanced second‐line treatment in benzodiazepine‐refractory convulsive status epilepticus in children

Ketamine as advanced second‐line treatment in benzodiazepine‐refractory convulsive status epilepticus in children

The Roles of Glutamate Receptors and Their Antagonists in Status Epilepticus, Refractory Status Epilepticus, and Super-Refractory Status Epilepticus

Phenobarbital in super‐refractory status epilepticus (PIRATE): A retrospective, multicenter analysis

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