Drug selection, timing for refractory convulsive status epilepticus need improvement

WASHINGTON – The choice of antiepileptic drugs for the treatment of pediatric convulsive status epilepticus was highly variable, and treatment timing and escalation were less than ideal in a pediatric Status Epilepticus Research Group study.

The findings suggest there is "room for improvement" in the management of this serious, life-threatening condition through more timely administration of antiepileptic drugs (AEDs) and through quicker progression from one AED to the next, Dr. Tobias Loddenkemper reported at the annual meeting of the American Epilepsy Society.

The findings represent a first step in addressing the inadequacies in the care of children with refractory convulsive status epilepticus (RCSE), and they underscore the need for parental education and ensuring that rescue medications are available for children with an epilepsy diagnosis, as well as the need for improved management in the inpatient setting, said Dr. Loddenkemper of Boston Children’s Hospital.

The analysis of RCSE episodes in 81 children aged 1 month to 21 years (mean age, 2.5 years) who were treated in the intensive care unit at any of the 11 U.S. tertiary referral hospitals that comprise the pediatric Status Epilepticus Research Group (pSERG) network showed that most episodes (79%) had onset out of the hospital. The median time to emergency medical services arrival was 15 minutes, and the median time to hospital arrival was 47 minutes. The median times to various steps of treatment far exceeded current guideline recommendations, according to Dr. Loddenkemper:

• 30 minutes for the administration of a first benzodiazepine drug by intravenous bolus dosing; guidelines call for treatment within 5 minutes.

• 69 minutes for the administration of a second drug; guidelines recommend 5-10 minutes.

• 120 minutes for the administration of a second non-benzodiazepine drug; guidelines call for 20-30 minutes.

• 180 minutes for the continuous infusion of anesthetic drugs; guidelines call for continuous infusion to begin within 30-70 minutes.

However, delays also occurred for in-hospital RCSE episodes, he said. The median times to first and second drugs for in-hospital episodes were 10 and 20 minutes, respectively.

Of the 81 patients included in the analysis, 75% were intubated and only 67% returned to baseline functioning after the RCSE episode. Four patients (4.9%) died.

"This [mortality] signifies how important this is," he said of RCSE during a press briefing at the meeting, noting that it is the most severe form of epilepsy, and that prompt and appropriate treatment is important for improving outcomes.

Of particular concern was the finding that most of the children in this study had a preexisting diagnosis of epilepsy, yet only half received a rescue medication in the outpatient setting.

"Technically, they should have had some kind of rescue medications, but they either were not given or were not prescribed," he said.

As for drug selection in this study, the most frequent choice of first benzodiazepine was lorazepam in 56% of cases, followed by diazepam in about a third of patients, and midazolam and clobazam in just a few cases each. The choice for a second benzodiazepine was most often lorazepam in 70% of cases, followed by midazolam and diazepam.

The choice of a first non-benzodiazepine drug was fosphenytoin in 52% of cases, followed by phenytoin and levetiracetam, Dr. Loddenkemper said. Phenobarbital, valproate, rufinamide, and propofol were also among the choices for first non-benzodiazepine drug. The choice of a second non-benzodiazepine drug was phenobarbital in 45% of cases, followed by levetiracetam, fosphenytoin, valproate, phenytoin, and propofol. The choice of anesthetic drug for continuous drug infusion was midazolam in 75% of cases. Other drugs used for continuous infusion included pentobarbital, propofol, and isoflurane. Pentobarbital was the first choice for second drug for infusion in 38% of cases.

The first choice of drug in each of those stages of treatment was generally within guidelines, but the high variability with respect to drug choices is concerning, he said.

All consecutive children presenting with RCSE to the ICUs in the pSERG network were included as long as they either failed at least two AEDs or required continuous infusion of an AED drug to abort their seizures.

Quicker progression from one drug to another in RCSE cases and coadministration of the first and second drugs are among strategies for improving outcomes. "Maybe we just have to treat faster," he suggested.

He also suggested that care could be improved by the use of dedicated treatment algorithms and dedicated teams of physicians who take care of patients with RCSE – much like the successful model for stroke care used at many hospitals in the United States.

Additional analysis from this study could shed more light on methods for improving outcomes. Data from an additional 46 patients are currently being analyzed, Dr. Loddenkemper said.

This study was funded by the American Epilepsy Society Infrastructure Award and the Epilepsy Foundation of America. Dr. Loddenkemper reported receiving research funding from Eisai and Lundbeck.

WASHINGTON – The choice of antiepileptic drugs for the treatment of pediatric convulsive status epilepticus was highly variable, and treatment timing and escalation were less than ideal in a pediatric Status Epilepticus Research Group study.

The findings suggest there is "room for improvement" in the management of this serious, life-threatening condition through more timely administration of antiepileptic drugs (AEDs) and through quicker progression from one AED to the next, Dr. Tobias Loddenkemper reported at the annual meeting of the American Epilepsy Society.

The findings represent a first step in addressing the inadequacies in the care of children with refractory convulsive status epilepticus (RCSE), and they underscore the need for parental education and ensuring that rescue medications are available for children with an epilepsy diagnosis, as well as the need for improved management in the inpatient setting, said Dr. Loddenkemper of Boston Children’s Hospital.

The analysis of RCSE episodes in 81 children aged 1 month to 21 years (mean age, 2.5 years) who were treated in the intensive care unit at any of the 11 U.S. tertiary referral hospitals that comprise the pediatric Status Epilepticus Research Group (pSERG) network showed that most episodes (79%) had onset out of the hospital. The median time to emergency medical services arrival was 15 minutes, and the median time to hospital arrival was 47 minutes. The median times to various steps of treatment far exceeded current guideline recommendations, according to Dr. Loddenkemper:

• 30 minutes for the administration of a first benzodiazepine drug by intravenous bolus dosing; guidelines call for treatment within 5 minutes.

• 69 minutes for the administration of a second drug; guidelines recommend 5-10 minutes.

• 120 minutes for the administration of a second non-benzodiazepine drug; guidelines call for 20-30 minutes.

• 180 minutes for the continuous infusion of anesthetic drugs; guidelines call for continuous infusion to begin within 30-70 minutes.

However, delays also occurred for in-hospital RCSE episodes, he said. The median times to first and second drugs for in-hospital episodes were 10 and 20 minutes, respectively.

Of the 81 patients included in the analysis, 75% were intubated and only 67% returned to baseline functioning after the RCSE episode. Four patients (4.9%) died.

"This [mortality] signifies how important this is," he said of RCSE during a press briefing at the meeting, noting that it is the most severe form of epilepsy, and that prompt and appropriate treatment is important for improving outcomes.

Of particular concern was the finding that most of the children in this study had a preexisting diagnosis of epilepsy, yet only half received a rescue medication in the outpatient setting.

"Technically, they should have had some kind of rescue medications, but they either were not given or were not prescribed," he said.

As for drug selection in this study, the most frequent choice of first benzodiazepine was lorazepam in 56% of cases, followed by diazepam in about a third of patients, and midazolam and clobazam in just a few cases each. The choice for a second benzodiazepine was most often lorazepam in 70% of cases, followed by midazolam and diazepam.

The choice of a first non-benzodiazepine drug was fosphenytoin in 52% of cases, followed by phenytoin and levetiracetam, Dr. Loddenkemper said. Phenobarbital, valproate, rufinamide, and propofol were also among the choices for first non-benzodiazepine drug. The choice of a second non-benzodiazepine drug was phenobarbital in 45% of cases, followed by levetiracetam, fosphenytoin, valproate, phenytoin, and propofol. The choice of anesthetic drug for continuous drug infusion was midazolam in 75% of cases. Other drugs used for continuous infusion included pentobarbital, propofol, and isoflurane. Pentobarbital was the first choice for second drug for infusion in 38% of cases.

The first choice of drug in each of those stages of treatment was generally within guidelines, but the high variability with respect to drug choices is concerning, he said.

All consecutive children presenting with RCSE to the ICUs in the pSERG network were included as long as they either failed at least two AEDs or required continuous infusion of an AED drug to abort their seizures.

Quicker progression from one drug to another in RCSE cases and coadministration of the first and second drugs are among strategies for improving outcomes. "Maybe we just have to treat faster," he suggested.

He also suggested that care could be improved by the use of dedicated treatment algorithms and dedicated teams of physicians who take care of patients with RCSE – much like the successful model for stroke care used at many hospitals in the United States.

Additional analysis from this study could shed more light on methods for improving outcomes. Data from an additional 46 patients are currently being analyzed, Dr. Loddenkemper said.

This study was funded by the American Epilepsy Society Infrastructure Award and the Epilepsy Foundation of America. Dr. Loddenkemper reported receiving research funding from Eisai and Lundbeck.

WASHINGTON – The choice of antiepileptic drugs for the treatment of pediatric convulsive status epilepticus was highly variable, and treatment timing and escalation were less than ideal in a pediatric Status Epilepticus Research Group study.

The findings suggest there is "room for improvement" in the management of this serious, life-threatening condition through more timely administration of antiepileptic drugs (AEDs) and through quicker progression from one AED to the next, Dr. Tobias Loddenkemper reported at the annual meeting of the American Epilepsy Society.

The findings represent a first step in addressing the inadequacies in the care of children with refractory convulsive status epilepticus (RCSE), and they underscore the need for parental education and ensuring that rescue medications are available for children with an epilepsy diagnosis, as well as the need for improved management in the inpatient setting, said Dr. Loddenkemper of Boston Children’s Hospital.

The analysis of RCSE episodes in 81 children aged 1 month to 21 years (mean age, 2.5 years) who were treated in the intensive care unit at any of the 11 U.S. tertiary referral hospitals that comprise the pediatric Status Epilepticus Research Group (pSERG) network showed that most episodes (79%) had onset out of the hospital. The median time to emergency medical services arrival was 15 minutes, and the median time to hospital arrival was 47 minutes. The median times to various steps of treatment far exceeded current guideline recommendations, according to Dr. Loddenkemper:

• 30 minutes for the administration of a first benzodiazepine drug by intravenous bolus dosing; guidelines call for treatment within 5 minutes.

• 69 minutes for the administration of a second drug; guidelines recommend 5-10 minutes.

• 120 minutes for the administration of a second non-benzodiazepine drug; guidelines call for 20-30 minutes.

• 180 minutes for the continuous infusion of anesthetic drugs; guidelines call for continuous infusion to begin within 30-70 minutes.

However, delays also occurred for in-hospital RCSE episodes, he said. The median times to first and second drugs for in-hospital episodes were 10 and 20 minutes, respectively.

Of the 81 patients included in the analysis, 75% were intubated and only 67% returned to baseline functioning after the RCSE episode. Four patients (4.9%) died.

"This [mortality] signifies how important this is," he said of RCSE during a press briefing at the meeting, noting that it is the most severe form of epilepsy, and that prompt and appropriate treatment is important for improving outcomes.

Of particular concern was the finding that most of the children in this study had a preexisting diagnosis of epilepsy, yet only half received a rescue medication in the outpatient setting.

"Technically, they should have had some kind of rescue medications, but they either were not given or were not prescribed," he said.

As for drug selection in this study, the most frequent choice of first benzodiazepine was lorazepam in 56% of cases, followed by diazepam in about a third of patients, and midazolam and clobazam in just a few cases each. The choice for a second benzodiazepine was most often lorazepam in 70% of cases, followed by midazolam and diazepam.

The choice of a first non-benzodiazepine drug was fosphenytoin in 52% of cases, followed by phenytoin and levetiracetam, Dr. Loddenkemper said. Phenobarbital, valproate, rufinamide, and propofol were also among the choices for first non-benzodiazepine drug. The choice of a second non-benzodiazepine drug was phenobarbital in 45% of cases, followed by levetiracetam, fosphenytoin, valproate, phenytoin, and propofol. The choice of anesthetic drug for continuous drug infusion was midazolam in 75% of cases. Other drugs used for continuous infusion included pentobarbital, propofol, and isoflurane. Pentobarbital was the first choice for second drug for infusion in 38% of cases.

The first choice of drug in each of those stages of treatment was generally within guidelines, but the high variability with respect to drug choices is concerning, he said.

All consecutive children presenting with RCSE to the ICUs in the pSERG network were included as long as they either failed at least two AEDs or required continuous infusion of an AED drug to abort their seizures.

Quicker progression from one drug to another in RCSE cases and coadministration of the first and second drugs are among strategies for improving outcomes. "Maybe we just have to treat faster," he suggested.

He also suggested that care could be improved by the use of dedicated treatment algorithms and dedicated teams of physicians who take care of patients with RCSE – much like the successful model for stroke care used at many hospitals in the United States.

Additional analysis from this study could shed more light on methods for improving outcomes. Data from an additional 46 patients are currently being analyzed, Dr. Loddenkemper said.

This study was funded by the American Epilepsy Society Infrastructure Award and the Epilepsy Foundation of America. Dr. Loddenkemper reported receiving research funding from Eisai and Lundbeck.