Tag Archives: Anticonvulsants

Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital. (Emrath)

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Tasker RC, et al. Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital. Pediatr Crit Care Med. 2016 Oct;17(10):968-975.

OBJECTIVE: To describe pediatric patients with convulsive refractory status epilepticus in whom there is intention to use an IV anesthetic for seizure control.

DESIGN: Two-year prospective observational study evaluating patients (age range, 1 mo to 21 yr) with refractory status epilepticus 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 refractory status epilepticus (median age, 3.7 yr; 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment.

MAIN RESULTS: The median (interquartile range) ICU 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] hr; 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 nonresponders, transition to a second agent occurred after a median of 1 day. Most patients (94%) experienced seizure termination with these two therapies.

CONCLUSIONS: Midazolam and pentobarbital remain the mainstay of continuous infusion therapy for refractory status epilepticus 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.

Variation in Anticonvulsant Selection and Electroencephalographic Monitoring Following Severe Traumatic Brain Injury in Children-Understanding Resource Availability in Sites Participating in a Comparative Effectiveness Study. (Williams)

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Kurz JE, et al. Variation in Anticonvulsant Selection and Electroencephalographic Monitoring Following Severe Traumatic Brain Injury in Children-Understanding Resource Availability in Sites Participating in a Comparative Effectiveness Study. Pediatr Crit Care Med. 2016 Jul; 17(7):649-657.

OBJECTIVES: Early posttraumatic seizures may contribute to worsened outcomes after traumatic brain injury. Evidence to guide the evaluation and management of early posttraumatic seizures in children is limited. We undertook a survey of current practices of continuous electroencephalographic monitoring, seizure prophylaxis, and the management of early posttraumatic seizures to provide essential information for trial design and the development of posttraumatic seizure management pathways.

DESIGN: Surveys were sent to site principal investigators at all 43 sites participating in the Approaches and Decisions in Acute Pediatric TBI trial at the time of the survey. Surveys consisted of 12 questions addressing strategies to 1) implement continuous electroencephalographic monitoring, 2) posttraumatic seizure prophylaxis, 3) treat acute posttraumatic seizures, 4) treat status epilepticus and refractory status epilepticus, and 5) monitor antiseizure drug levels.

SETTING: Institutions comprised a mixture of free-standing children’s hospitals and university medical centers across the United States and Europe.

SUBJECTS: Site principal investigators of the Approaches and Decisions in Acute Pediatric TBI trial.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Continuous electroencephalographic monitoring was available in the PICU in the overwhelming majority of clinical sites (98%); however, the plans to operationalize such monitoring for children varied considerably. A similar majority of sites report that administration of prophylactic antiseizure medications is anticipated in children (93%); yet, a minority reports that a specified protocol for treatment of posttraumatic seizures is in place (43%). Reported medication choices varied substantially between sites, but the majority of sites reported pentobarbital for refractory status epilepticus (81%). The presence of treatment protocols for seizure prophylaxis, early posttraumatic seizures, posttraumatic status epilepticus, and refractory status epilepticus was associated with decreased reported medications (all p < 0.05).

CONCLUSIONS: This study reports the current management practices for early posttraumatic seizures in select academic centers after pediatric severe traumatic brain injury. The substantial variation in continuous electroencephalographic monitoring implementation, choice of seizure prophylaxis medications, and management of early posttraumatic seizures across institutions was reported, signifying the areas of clinical uncertainty that will help provide focused design of clinical trials. Although sites with treatment protocols reported a decreased number of medications for the scenarios described, completion of the Approaches and Decisions in Acute Pediatric TBI trial will be able to determine if these protocols lead to decreased variability in medication administration in children at the clinical sites.

Prevalence of Early Posttraumatic Seizures in Children With Moderate to Severe Traumatic Brain Injury Despite Levetiracetam Prophylaxis. (Coleman)

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Chung MG, O’Brien NF. Prevalence of Early Posttraumatic Seizures in Children With Moderate to Severe Traumatic Brain Injury Despite Levetiracetam Prophylaxis. Pediatr Crit Care Med. 2015 Dec 11. [Epub ahead of print]

OBJECTIVES: To evaluate the prevalence of early seizures after levetiracetam prophylaxis in children with moderate to severe traumatic brain injury.

DESIGN: Prospective observational study.

SETTING: Level 1 pediatric trauma center.

PATIENTS: We enrolled 34 patients between the ages of 0-18 years with moderate to severe traumatic brain injury admitted to the PICU at a level 1 trauma center who received levetiracetam for early posttraumatic seizure prophylaxis.

MEASUREMENTS AND MAIN RESULTS: Primary outcome was the prevalence of early posttraumatic seizures that were defined as clinical seizures within 7 days of injury. In 6 of 34 patients (17%), clinical seizures developed despite levetiracetam prophylaxis. An additional two patients had nonconvulsive seizures. This prevalence is similar to that reported in the literature in this patient population who do not receive seizure prophylaxis (20-53%) and is higher than that in patients who receive phenytoin prophylaxis (2-15%). Patients with early posttraumatic seizures were younger (median age, 4 mo) (p < 0.001) and more likely to have suffered from abusive head trauma (p < 0.0004).

CONCLUSIONS: Early clinical posttraumatic seizures occurred frequently in children with moderate to severe traumatic brain injury despite seizure prophylaxis with levetiracetam. Younger children and those with abusive head trauma were at increased risk of seizures. Further studies are needed to evaluate the efficacy of levetiracetam before it is routinely used for seizure prophylaxis in these children, particularly in young children and those who have suffered from abusive head trauma.