Efficacy and safety of ketamine in refractory status epilepticus in children

From the Pediatric Neurology Unit (A.R., L.I., T.P., R.G.) and Intensive Care Unit (M.L., C.C., L.M.), Children's Hospital A. Meyer, University of Firenze, Florence, Italy.
Neurology (Impact Factor: 8.29). 11/2012; 79(24). DOI: 10.1212/WNL.0b013e318278b685
Source: PubMed


OBJECTIVE: To evaluate the efficacy and safety of ketamine (KE) in the management of refractory convulsive status epilepticus (RSE) in children. METHODS: In November 2009, we started using KE for treating all children consecutively referred for RSE. Clinical and treatment data were analyzed. RESULTS: Between November 2009 and June 2011, 9 children with RSE received IV KE. In 8 patients, SE had persisted for more than 24 hours (super-refractory RSE), with a median of 6 days (mean 8.5 ± 7.5; range 2-26 days). Prior to KE administration, conventional anesthetics were used, including midazolam, thiopental, and propofol in 9, 5, and 4 patients each. Median dose of KE in continuous IV infusion was 40 gamma(μg)/kg/min (mean 36.5 ± 18.6 gamma[μg]/kg/min; range 10-60 gamma[μg]/kg/min). Midazolam was administered add-on to prevent emergence reactions. The use of KE was associated with resolution of RSE in 6 children. None of the patients experienced serious adverse events. Among the 3 individuals who did not respond to KE, 2 were cured by surgical removal of epileptogenic focal cortical dysplasia. CONCLUSION: In this small, open-label, unblinded series with no concurrent control group, KE appears effective and safe in treating RSE in children. Larger, randomized studies are needed to confirm data emerging from this preliminary observation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that IV KE can be effective in treating children with RSE (no statistical analysis was done).

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    • "Our series (Class IV of evidence), although small, provides further evidence of the efficacy of KE for treating RCSE in children and its safety profile [14]. Status epilepticus resolution was obtained in 14/19 RCSE episodes, and none of the 13 patients experienced serious adverse events. "
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    ABSTRACT: The purpose of this study was to report on the efficacy and safety of intravenous ketamine (KE) in refractory convulsive status epilepticus (RCSE) in children and highlight its advantages with particular reference to avoiding endotracheal intubation. Since November 2009, we have used a protocol to treat RCSE including intravenous KE in all patients referred to the Neurology Unit of the Meyer Children's Hospital. From November 2009 to February 2015, 13 children (7 females; age: 2months-11years and 5months) received KE. Eight patients were treated once, two were treated twice, and the remaining three were treated 3 times during different RCSE episodes, for a total of 19 treatments. Most of the RCSE episodes were generalized (14/19). A malformation of cortical development was the most frequent etiology (4/13 children). Ketamine was administered from a minimum of 22h to a maximum of 17days, at doses ranging from 7 to 60mcg/kg/min, obtaining a resolution of the RCSE in 14/19 episodes. Five patients received KE in lieu of conventional anesthetics, thus, avoiding endotracheal intubation. Ketamine was effective in 4 of them. Suppression-burst pattern was observed after the initial bolus of 3mg/kg in the majority of the responder RCSE episodes (10/14). Ketamine is effective in treating RCSE and represents a practical alternative to conventional anesthetics for the treatment of RCSE. Its use avoids the pitfalls and dangers of endotracheal intubation, which is known to worsen RCSE prognosis. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.
    Epilepsy & Behavior 07/2015; 49. DOI:10.1016/j.yebeh.2015.06.019 · 2.26 Impact Factor
    • "Additional agents whose use remains controversial in patient with seizure disorders include ketamine, etomidate, and the synthetic opioids including remifentanil.[16] While it has been generally recommended that ketamine is contraindicated in patients at risk for seizure activity, the most recent literature has demonstrated the anticonvulsant effect of this agent and even used it to treat status epilepticus thereby further confounding this issue.[1718] Given these concerns, we chose to use a combination of sevoflurane, propofol, and the opioids, fentanyl, and hydromorphone for maintenance of anesthesia in our patient. "
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    ABSTRACT: The neuronal ceroid lipofuscinoses (NCL) are a group of inherited, autosomal recessive, and progressive neurodegenerative diseases, which result from an enzymatic defect or the deficiency of a transmembrane protein, leading to the accumulation of lipopigments (lipofuscin) in various tissues. NCL results in the impairment of function in several end-organs including the central nervous system with loss of cognitive and motor function, myoclonus, and intractable seizures. Additional involvement includes the cardiovascular system with arrhythmias and bradycardia as well as impairment of thermoregulation leading to perioperative hypothermia. Given the complexity of the end-organ involvement and the progressive nature of the disorder, the anesthetic care of such patients can be challenging. Till date, there are a limited number of reports regarding the anesthetic management of patients with NCL. We present an 18-year-old patient with NCL who required anesthetic care during replacement of a vagal nerve stimulator. Previous reports of anesthetic care for these patients are reviewed, the end-organ involvement of NCL discussed, and options for anesthetic care presented.
    07/2013; 7(3):336-40. DOI:10.4103/1658-354X.115329
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    ABSTRACT: Refractory status epilepticus (RSE) occurs when status epilepticus (SE) fails to respond to appropriate therapy with typical antiepileptic drugs (AEDs). Animal studies have shown ketamine to be a highly efficacious agent in this setting, but very few case reports describe use of ketamine in human SE or RSE. We report a retrospective review of 11 patients who were treated for RSE with ketamine infusion in addition to other standard AEDs over a nine-year period. Data collection included age, gender, history of epilepsy, etiology of RSE, daily dose of ketamine, co-therapeutic agents, duration of seizures, treatment response, and disposition. RSE was successfully terminated in all 11 patients treated with ketamine. Dosing ranged from 0.45mg/kg/h to 2.1mg/kg/h based upon the preference of the treating clinician and response to therapy, with maximal daily doses ranging from 1392mg to 4200mg. Ketamine was the last AED used prior to resolution of RSE in 7/11 (64%) cases. In the remaining four cases, one other AED was added after ketamine infusion had begun. Time from ketamine initiation to seizure cessation ranged from 4 to 28 days (mean=9.8, SD=8.9). In 7/11 patients, RSE was resolved within one week of starting therapy. Administration of ketamine was uniformly associated with improvement in hemodynamic stability. Six of the seven patients (85%) who required vasopressors during early treatment for RSE were able to be weaned from vasopressors during ketamine infusion. No acute adverse effects were noted. These findings suggest that ketamine may be a safe and efficacious adjunctive agent in the treatment of RSE.
    Epilepsy research 01/2013; 105(1-2). DOI:10.1016/j.eplepsyres.2013.01.007 · 2.02 Impact Factor
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