After evaluating this article, participants will be able to:
1. Incorporate strategies into practice for the management of status epilepticus
2. Develop strategies to effectively utilize newer anticonvultants in the acute management of seizures
Pediatric seizures are a common emergency department complaint. The prior definition of status epilepticus (SE) was: “More than 30 minutes of continuous seizure activity or two or more sequential seizures without full recovery of consciousness between seizures.” However, many providers believed that a shorter period of seizure activity could result in neuronal injury and that seizure self-termination is unlikely after 5 minutes. Lowenstein et al, have suggested a duration of longer than 5 minutes as part of the a criterion for SE, if the seizure type is one in which typical generalized convulsive seizures resolve spontaneously after 3-5 minutes.(Lowenstein DH, Bleck T, Macdonald RL. It’s time to revise the definition of status epilepticus. Epilepsia. Jan 1999;40(1):120-2)
It has become increasingly more important for emergency providers to rapidly cease seizure activity in order to prevent neurologic injury. This article will review options for acute anti-epileptic agents beyond the standard therapies of phenobarbital, phenytoin and fosphenytoin.
Q. If intravenous access is not available, how good are intramuscular benzodiazepines?
A. Intramuscular midazolam was shown in this trial to be an acceptable alternative route for acute seizure control
Citation : Silbergleit R, Durkalski V, Lowenstein D, et al Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012 Feb 16;366(7):591-600.
BACKGROUND: Early termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular route.
METHODS: This double-blind, randomized, noninferiority trial compared the efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epilepticus treated by paramedics. Subjects whose convulsions had persisted for more than 5 minutes and who were still convulsing after paramedics arrived were given the study medication by either intramuscular autoinjector or intravenous infusion. The primary outcome was absence of seizures at the time of arrival in the emergency department without the need for rescue therapy. Secondary outcomes included endotracheal intubation, recurrent seizures, and timing of treatment relative to the cessation of convulsive seizures. This trial tested the hypothesis that intramuscular midazolam was noninferior to intravenous lorazepam by a margin of 10 percentage points.
RESULTS: At the time of arrival in the emergency department, seizures were absent without rescue therapy in 329 of 448 subjects (73.4%) in the intramuscular-midazolam group and in 282 of 445 (63.4%) in the intravenous-lorazepam group (absolute difference, 10 percentage points; 95% confidence interval, 4.0 to 16.1; P<0.001 for both noninferiority and superiority). The two treatment groups were similar with respect to need for endotracheal intubation (14.1% of subjects with intramuscular midazolam and 14.4% with intravenous lorazepam) and recurrence of seizures (11.4% and 10.6%, respectively). Among subjects whose seizures ceased before arrival in the emergency department, the median times to active treatment were 1.2 minutes in the intramuscular-midazolam group and 4.8 minutes in the intravenous-lorazepam group, with corresponding median times from active treatment to cessation of convulsions of 3.3 minutes and 1.6 minutes. Adverse-event rates were similar in the two groups.
CONCLUSIONS: For subjects in status epilepticus, intramuscular midazolam is at least as safe and effective as intravenous lorazepam for prehospital seizure cessation. (Funded by the National Institute of Neurological Disorders and Stroke and others; ClinicalTrials.gov number, ClinicalTrials.gov NCT00809146.).
Q. Is intravenous levetiracetam (Keppra) effective for acute status epilepticus management?
A. Intravenous levetiracetam is being used more frequently by neurologists for acute seizure management. However, the first line agents are still benzodiazepines.
Citation: Kirmani BF, Crisp ED, Kayani S, Rajab H.Role of intravenous levetiracetam in acute seizure management of children. Pediatr Neurol. 2009 Jul;41(1):37-9.
Abstract: Status epilepticus is defined as a seizure lasting beyond 30 minutes. Children with intractable epilepsy undergo frequent hospital admissions secondary to status epilepticus or because of acute exacerbation of seizures. Intravenous levetiracetam became available in August 2006 for use in patients aged above 16 years. There are insufficient data about the efficacy and safety of intravenous levetiracetam in children. We retrospectively analyzed data from children treated with intravenous levetiracetam for status epilepticus and acute exacerbation of seizures. We acquired data from our institution’s electronic medical records concerning patients with status epilepticus and acute exacerbation of seizures who received intravenous levetiracetam. Thirty-two patients (age range, 2 months to 18 years) had received a levetiracetam load of 25-50 mg/kg for status epilepticus. There were 17 (53.1%) males and 15 (46.8%) females. Response to intravenous levetiracetam in all patients was favorable. Status epilepticus ceased clinically and electrographically. Eighteen patients (56.5%) received intravenous levetiracetam after receiving fosphenytoin and Ativan with no response. No serious side effects were evident. Fifteen patients (46.8%) were discharged on levetiracetam monotherapy, and 9 (28.1%) received levetiracetam as adjunctive therapy after discharge from the hospital. Intravenous levetiracetam can be used adjunctively or as monotherapy in children with status epilepticus and acute exacerbation of seizures.
Q. Can intravenous valproate be used in status epilepticus?
A. In addition to Keppra, intravenous valproate has been shown to be effective in cessation of acute seizures. The next two citations reported that rapid intravenous infusion was safe in children.
Citation: Morton LD, O’Hara KA, Coots BP, Pellock JM. Safety of rapid intravenous valproate infusion in pediatric patients. Pediatr Neurol. 2007 Feb;36(2):81-3
Abstract: In order to investigate the safety of rapidly infused intravenous valproate in children with seizures, the drug was administered to 18 patients (age range, 1-16 years) at doses ranging from 7.5 to 41.5 mg/kg and rates of 1.5 to 11 mg/kg per minute. Forty-eight intravenous valproate doses were administered during 19 hospital admissions (range, 1-16 doses per admission). Only one adverse event was reported; a 9-year-old male experienced burning at the infusion site while receiving 660 mg intravenous valproate at 6 mg/kg per minute. The patient tolerated three subsequent infusions (one of 330 mg and two of 165 mg) at the same rate with no further discomfort. Electrocardiogram results, available for 18 admissions, revealed no arrhythmias, bradycardias, or hypotensive episodes. No abnormal laboratory results were reported. Rapid intravenous valproate infusion appears to be safe in pediatric patients
Citation: Yu KT, Mills S, Thompson N, Cunanan C. Safety and efficacy of intravenous valproate in pediatric status epilepticus and acute repetitive seizures. Epilepsia. 2003 May;44(5):724-6.
PURPOSE: To evaluate the safety and efficacy of intravenous valproate (VPA) loading in children with status epilepticus (SE) or acute repetitive seizures.
METHODS: Retrospective review was performed on 40 pediatric patients with intravenous VPA loading. Patients were classified into two groups: SE (n = 18) and acute repetitive seizures (n = 22). Thirty-one patients were VPA naïve and received a full loading dose of 25 mg/kg; nine had subtherapeutic plasma VPA levels and received a partial loading dose. Average infusion rate was 2.8 mg/kg/min. Heart rate and blood pressure were measured before, during, and after infusion.
RESULTS: Intravenous VPA loading stopped seizures in 18 patients with SE within 20 min. All 18 patients regained baseline mental status within 1 h of seizure cessation. Among 22 patients with acute repetitive seizures, only one had further seizures after VPA infusion. One patient in the SE group complained of transient tremors. No significant changes in blood pressure or heart rate were found in either group. Postinfusion plasma VPA levels ranged from 51 to 138 microg/ml (mean +/- SD = 88 +/- 21.5 microg/ml).
CONCLUSIONS: Intravenous VPA loading is safe and effective for treating acute seizure emergencies in children.
Summary: In the event that an intravenous line cannot be established in patients in status epilepticus, it is imperative to remember that alternative routes exist. Intramuscular midazolam can be administered in a dose of 0.2mg/kg. In addition, atomized or buccal midazolam can be given in a dose 0.2-0.5mg/kg. There is often substantial delay in the administration of antiepileptic agents due to the lack of an IV. With the risk of permanent neurologic injury, this is not an acceptable practice and providers should rapidly proceed to intraosseous line placement after first giving either intramuscular, nasalor buccal medication.
Dr. Ghazala Sharieff is the Division Director at the San Diego Rady Children’s Hospital Emergency Care Center.