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Intravenous Ketamine Bolus(es) for the Treatment of Status Epilepticus, Refractory Status Epilepticus, and Cluster Seizures: A Retrospective Study of 15 Dogs.

ABSTRACT: Status epilepticus (SE) and cluster seizures (CS) are common occurrences in veterinary neurology and frequent reasons of admission to veterinary hospitals. With prolonged seizure activity, gamma amino-butyric acid (GABA) receptors (GABAa receptors) become inactive, leading to a state of pharmacoresistance to benzodiazepines and other GABAergic medications, which is called refractory status epilepticus (RSE). Prolonged seizure activity is also associated with overexpression of N-methyl-D-aspartic (NMDA) receptors. Rodent models have shown the efficacy of ketamine (KET) in treating RSE, and its use has been reported in one canine case of RSE. Boluses of KET 5 mg/kg IV have become the preferred treatment for RSE in our hospital. A retrospective study was performed to evaluate and report our experience with KET IV bolus to treat prolonged and/or repeated seizure activity in cases of canine CS, SE, and RSE. A total of 15 dogs were retrieved, for 20 hospitalizations and 28 KET IV injections over 3 years. KET IV boluses were used 12 times for RSE (9 generalized seizures, 3 focal seizures) and KET terminated the episode of RSE 12/12 times (100%); however, seizures recurred 4/12 times (33%) within ?6 h of KET IV bolus. When used for CS apart from episodes of RSE, KET IV bolus was associated with termination of the CS episode only 4/14 times (29%). Only 4/28 (14%) KET IV boluses were associated with adverse effects imputable only to the use of KET. One dog experienced a short, self-limited seizure activity during administration of KET IV, which was most likely related to a pre-mature use of KET IV (i.e., before GABAergic resistance and NMDA receptor overexpression had taken place). This study indicates that KET 5 mg/kg IV bolus may be successful for the treatment of RSE in dogs.

SUBMITTER: Roynard P

PROVIDER: S-EPMC7925624 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Intravenous Ketamine Bolus(es) for the Treatment of Status Epilepticus, Refractory Status Epilepticus, and Cluster Seizures: A Retrospective Study of 15 Dogs.

Roynard Patrick P Bilderback Ann A Dewey Curtis Wells CW

Frontiers in veterinary science 20210217

Status epilepticus (SE) and cluster seizures (CS) are common occurrences in veterinary neurology and frequent reasons of admission to veterinary hospitals. With prolonged seizure activity, gamma amino-butyric acid (GABA) receptors (GABAa receptors) become inactive, leading to a state of pharmacoresistance to benzodiazepines and other GABAergic medications, which is called refractory status epilepticus (RSE). Prolonged seizure activity is also associated with overexpression of <i>N</i>-methyl-D-a ...[more]

PMID: 33681317

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Project description:BACKGROUND:Patients in refractory status epilepticus (RSE) may require treatment with continuous intravenous anesthetic drugs (cIVADs) for seizure control. The use of cIVADs, however, was recently associated with poor outcome in status epilepticus (SE), raising the question of whether cIVAD therapy should be delayed for attempts to halt seizures with repeated non-anesthetic antiepileptic drugs. In this study, we aimed to determine the impact of differences in therapeutic approaches on RSE outcome using timing of cIVAD therapy as a surrogate for treatment aggressiveness. METHODS:This was a retrospective cohort study over 14 years (n = 77) comparing patients with RSE treated with cIVADs within and after 48 h after RSE onset, and functional status at last follow-up was the primary outcome (good = return to premorbid baseline or modified Rankin Scale score of less than 3). Secondary outcomes included discharge functional status, in-hospital mortality, RSE termination, induction of burst suppression, use of thiopental, duration of RSE after initiation of cIVADs, duration of mechanical ventilation, and occurrence of super-refractory SE. Analysis was performed on the total cohort and on subgroups defined by RSE severity according to the Status Epilepticus Severity Score (STESS) and by the variables contained therein. RESULTS:Fifty-three (68.8%) patients received cIVADs within the first 48 h. Early cIVAD treatment was independently associated with good outcome (adjusted risk ratio [aRR] 3.175, 95% confidence interval [CI] 1.273-7.918; P = 0.013) as well as lower chance of both induction of burst suppression (aRR 0.661, 95% CI 0.507-0.861; P = 0.002) and use of thiopental (aRR 0.446, 95% CI 0.205-0.874; P = 0.043). RSE duration after cIVAD initiation was shorter in the early cIVAD cohort (hazard ratio 1.796, 95% CI 1.047-3.081; P = 0.033). Timing of cIVAD use did not impact the remaining secondary outcomes. Subgroup analysis revealed early cIVAD impact on the primary outcome to be driven by patients with STESS of less than?3. CONCLUSIONS:Patients with RSE treated with cIVADs may benefit from early initiation of such therapy.

Project description:BackgroundKetamine, as an anesthetic, has been considered for terminating status epilepticus (SE); however, due to the urgency and severity of the condition, there are currently no randomized controlled trials internationally assessing the efficacy of ketamine for treating super-refractory status epilepticus. Similarly, there appears to be a lack of systematic reviews addressing this topic in the literature. Therefore, this systematic review aims to explore the effectiveness and safety of ketamine for terminating super-refractory status epilepticus.MethodsWe conducted a systematic search on PubMed, EMBASE, and Web of Science databases. Manuscripts unrelated to the research on super-refractory status epilepticus were excluded, as were manuscripts published in non-English languages. The quality assessment and risk of bias were evaluated using the MINORS criteria. Data extraction was limited to qualitative synthesis due to the unsuitability of the data for meta-analysis.ResultsOut of 782 studies retrieved from electronic databases, 11 met the inclusion criteria. Among them, 10 studies were retrospective, and 1 study was prospective. Patient data for inclusion were sourced from the case registries of the researchers' respective hospitals. Across all included studies, the administration of ketamine significantly reduced the duration of status epilepticus and demonstrated higher safety compared to patients not receiving ketamine treatment for super-refractory status epilepticus. Additionally, early administration of ketamine correlated with improved treatment outcomes. The risk of bias across all studies was deemed low.ConclusionThis systematic review suggests that ketamine may be a feasible treatment option for super-refractory status epilepticus. However, given the critical nature of super-refractory status epilepticus, clinicians should prioritize its termination over evaluating the efficacy of specific medications, ensuring patient safety remains paramount. If feasible in real-world medical settings, future research should focus on designing randomized controlled trials to observe the specific efficacy and mechanisms of ketamine. Careful validation is necessary before considering ketamine as a first-line treatment for super-refractory status epilepticus.

Dataset Information

Intravenous Ketamine Bolus(es) for the Treatment of Status Epilepticus, Refractory Status Epilepticus, and Cluster Seizures: A Retrospective Study of 15 Dogs.

Publications

Intravenous Ketamine Bolus(es) for the Treatment of Status Epilepticus, Refractory Status Epilepticus, and Cluster Seizures: A Retrospective Study of 15 Dogs.

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