Etiology, clinical course and response to the treatment of status epilepticus in children: A 16-year single-center experience based on 602 episodes of status epilepticus

Kravljanac, Ružica; Djurić, Milena; Janković, Bojan; Pekmezović, Tatjana

doi:10.1016/j.ejpn.2015.05.007

Cited by 39 publications

(47 citation statements)

References 23 publications

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“…Bolus dosing and initial infusion rates for midazolam were similar to those reported in previous studies, [11–23] with a median dose of 0.11 mg/kg (average in the literature 0.15 – 0.50 mg/kg) and 1.7 mcg/kg/min (average in the literature 1 – 2 mcg/kg/min) respectively. However, previous studies identified an apparent discrepancy: treatment dosing from studies using EEG monitoring to guide therapy [13,19] used considerably higher doses of midazolam when compared with studies using a clinical endpoint to guide treatment (10.7 mcg/kg/min versus 2.8 mcg/kg/min).…”

Section: Discussionsupporting

confidence: 82%

See 1 more Smart Citation

Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital*

Tasker

Goodkin

Fernández

et al. 2016

Pediatric Critical Care Medicine

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Objective To describe pediatric patients with convulsive refractory status epilepticus (RSE) in whom there is intention-to-use an intravenous anesthetic for seizure control. Design Two-year prospective observational study evaluating patients (age range one month to 21 years) with RSE not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent. Setting Nine pediatric hospitals in the United States. Patients In a cohort of 111 patients with RSE (median age 3.7 years, 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment. Main Results The median (interquartile range, IQR) intensive care unit length-of-stay was 10 (3–20) days. Up to four ‘cycles’ of serial anesthetic therapy were used and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9–34) hours for the first cycle, and longer when a second cycle was required (30 [4,−120] hours, p=0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam non-responders, transition to a second agent occurred after a median of one day. Most patients (94%) experienced seizure termination with these two therapies. Conclusions Midazolam and pentobarbital remains the mainstay of continuous infusion therapy for RSE in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure, may be possible in a multicenter multinational study.

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Section: Discussionsupporting

confidence: 82%

“…[12–23] The current prospective pSERG cohort from 2011 to 2013 adds contemporary data to this literature. The proportion of RSE patients presenting to emergency services needing midazolam infusion is substantial, occurring in 29% to 47% of patients (95% CI), a finding that may have implications for hospital emergency services.…”

Section: Discussionmentioning

confidence: 99%

Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital*

Tasker

Goodkin

Fernández

et al. 2016

Pediatric Critical Care Medicine

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“…The number of patients per study ranged from as small as one to as large as 358 children 127 and 339 adults. 128 Efficacy (as determined by cessation of clinical or electrographic RSE when MDZ was the last ASM added) was 56% in neonates. 126 Efficacy was 46.7% to 100% (median = 89%, regardless of sample size) across the studies in children.…”

Section: Resultsmentioning

confidence: 99%

Treatment of Refractory Convulsive Status Epilepticus: A Comprehensive Review by the American Epilepsy Society Treatments Committee

et al. 2020

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Purpose: Established tonic–clonic status epilepticus (SE) does not stop in one-third of patients when treated with an intravenous (IV) benzodiazepine bolus followed by a loading dose of a second antiseizure medication (ASM). These patients have refractory status epilepticus (RSE) and a high risk of morbidity and death. For patients with convulsive refractory status epilepticus (CRSE), we sought to determine the strength of evidence for 8 parenteral ASMs used as third-line treatment in stopping clinical CRSE. Methods: A structured literature search (MEDLINE, Embase, CENTRAL, CINAHL) was performed to identify original studies on the treatment of CRSE in children and adults using IV brivaracetam, ketamine, lacosamide, levetiracetam (LEV), midazolam (MDZ), pentobarbital (PTB; and thiopental), propofol (PRO), and valproic acid (VPA). Adrenocorticotropic hormone (ACTH), corticosteroids, intravenous immunoglobulin (IVIg), magnesium sulfate, and pyridoxine were added to determine the effectiveness in treating hard-to-control seizures in special circumstances. Studies were evaluated by predefined criteria and were classified by strength of evidence in stopping clinical CRSE (either as the last ASM added or compared to another ASM) according to the 2017 American Academy of Neurology process. Results: No studies exist on the use of ACTH, corticosteroids, or IVIg for the treatment of CRSE. Small series and case reports exist on the use of these agents in the treatment of RSE of suspected immune etiology, severe epileptic encephalopathies, and rare epilepsy syndromes. For adults with CRSE, insufficient evidence exists on the effectiveness of brivaracetam (level U; 4 class IV studies). For children and adults with CRSE, insufficient evidence exists on the effectiveness of ketamine (level U; 25 class IV studies). For children and adults with CRSE, it is possible that lacosamide is effective at stopping RSE (level C; 2 class III, 14 class IV studies). For children with CRSE, insufficient evidence exists that LEV and VPA are equally effective (level U, 1 class III study). For adults with CRSE, insufficient evidence exists to support the effectiveness of LEV (level U; 2 class IV studies). Magnesium sulfate may be effective in the treatment of eclampsia, but there are only case reports of its use for CRSE. For children with CRSE, insufficient evidence exists to support either that MDZ and diazepam infusions are equally effective (level U; 1 class III study) or that MDZ infusion and PTB are equally effective (level U; 1 class III study). For adults with CRSE, insufficient evidence exists to support either that MDZ infusion and PRO are equally effective (level U; 1 class III study) or that low-dose and high-dose MDZ infusions are equally effective (level U; 1 class III study). For children and adults with CRSE, insufficient evidence exists to support that MDZ is effective as the last drug added (level U; 29 class IV studies). For adults with CRSE, insufficient evidence exists to support that PTB and PRO are equally effective (level U; 1 class III study). For adults and children with CRSE, insufficient evidence exists to support that PTB is effective as the last ASM added (level U; 42 class IV studies). For CRSE, insufficient evidence exists to support that PRO is effective as the last ASM used (level U; 26 class IV studies). No pediatric-only studies exist on the use of PRO for CRSE, and many guidelines do not recommend its use in children aged <16 years. Pyridoxine-dependent and pyridoxine-responsive epilepsies should be considered in children presenting between birth and age 3 years with refractory seizures and no imaging lesion or other acquired cause of seizures. For children with CRSE, insufficient evidence exists that VPA and diazepam infusion are equally effective (level U, 1 class III study). No class I to III studies have been reported in adults treated with VPA for CRSE. In comparison, for children and adults with established convulsive SE (ie, not RSE), after an initial benzodiazepine, it is likely that loading doses of LEV 60 mg/kg, VPA 40 mg/kg, and fosphenytoin 20 mg PE/kg are equally effective at stopping SE (level B, 1 class I study). Conclusions: Mostly insufficient evidence exists on the efficacy of stopping clinical CRSE using brivaracetam, lacosamide, LEV, valproate, ketamine, MDZ, PTB, and PRO either as the last ASM or compared to others of these drugs. Adrenocorticotropic hormone, IVIg, corticosteroids, magnesium sulfate, and pyridoxine have been used in special situations but have not been studied for CRSE. For the treatment of established convulsive SE (ie, not RSE), LEV, VPA, and fosphenytoin are likely equally effective, but whether this is also true for CRSE is unknown. Triple-masked, randomized controlled trials are needed to compare the effectiveness of parenteral anesthetizing and nonanesthetizing ASMs in the treatment of CRSE.

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“…Furthermore, other retrospective studies not specifically designed to look at CLB in SE have reported conflicting results. Although 3 studies have reported treatment failure with CLB, 2 studies have reported treatment success . Due to the retrospective nature of those studies it is unknown whether remission was due to the effect of CLB, or rather its effect in combination with other AEDs.…”

Section: Resultsmentioning

confidence: 99%

“…Although 3 studies have reported treatment failure with CLB, [13][14][15] 2 studies have reported treatment success. 16,17 Due to the retrospective nature of those studies it is unknown whether remission was due to the effect of CLB, or rather its effect in combination with other AEDs.…”

Section: Efficacy Of Clobazam In Status Epilepticusmentioning

confidence: 99%

Systematic review of clobazam use in patients with status epilepticus

Mahmoud

Rans

2018

Epilepsia Open

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SummaryClobazam (CLB) is a commonly used oral antiepileptic drug (AED) that has been shown to be effective in various forms of epilepsy. Given its distinct 1,5‐benzodiazepine structure, rapid absorption, minimal drug interactions, and favorable safety profile, CLB displays unique properties when compared to other commonly used benzodiazepines. Recent evidence has shown that CLB may demonstrate therapeutic efficacy in status epilepticus (SE). The objective of this systematic review was to summarize the available evidence pertaining to the efficacy of CLB use in SE. An electronic literature search of Medline (1946 to November 6, 2017), Embase (1974 to November 6, 2017), and the Cochrane Library (1999 to November 6, 2017) databases was performed to identify reports of CLB use in SE. After screening and full text review, a total of 15 articles were included: 8 retrospective studies, 2 case series, and 5 case reports. Efficacy rates for CLB have varied among reports. Overall, based on the retrospective studies, a total of 76 patients with SE have been reported. CLB was introduced within 2–4 days from SE onset and has been reported to contribute to remission in 36 patients (47%). CLB maintenance dose ranged from 10 to 60 mg/day. However, the results need to be interpreted carefully because SE patients are a heterogeneous group with different etiologies and disease severities, and the response to CLB might vary in different patient population or seizure types. In conclusion, there is not sufficient evidence to determine the safety and efficacy of clobazam in the setting of SE. However, the current limited evidence combined with the unique characteristics of CLB suggest that the drug might be considered as an add‐on option in SE patients, with a suggested dosage range of 10–60 mg/day. Prospective studies are needed to fully establish the role of CLB in the management of SE.

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Etiology, clinical course and response to the treatment of status epilepticus in children: A 16-year single-center experience based on 602 episodes of status epilepticus

Cited by 39 publications

References 23 publications

Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital*

Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital*

Treatment of Refractory Convulsive Status Epilepticus: A Comprehensive Review by the American Epilepsy Society Treatments Committee

Systematic review of clobazam use in patients with status epilepticus

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