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Paper text:
refractory status epilepticus ( rse ) is defined as seizures that are nonresponsive to adequate initial anti - epileptic therapy and require a continuous infusion of an antiepileptic medication or administration of inhalation anesthetic agent to stop the seizure activity .
the care of children with rse is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children .
the use of a pentobarbital infusion in the management of rse has shown to be associated with a high morbidity and mortality .
the current study describes a single center experience of management of rse with the use of midazolam and pentobarbital .
in this retrospective cohort study , children ( age : 0 - 21 years ) admitted to a tertiary - care pediatric intensive care unit with rse , over a 3-year period , were identified and included .
demographic and clinical data were collected from the hospital administrative database and electronic patient healthcare records . all children who continued to have either clinical or electrical seizure activity despite initial treatment with lorazepam , diazepam , phenytoin , and phenobarbital and required a continuous anti - epileptic medication infusion to control their seizure activity
children who had recurrent seizures and required a continuous infusion of anti - epileptic medication were included .
patients who were admitted with status epilepticus and did not require a continuous infusion to control their seizures were excluded from the study .
patients who were transferred from an outside institution , intubated and on a benzodiazepine infusion , and whose seizures had terminated were also excluded . all children who receive pentobarbital were monitored with a continuous electroencephalogram ( eeg ) recording .
outcome of children who required continuous pentobarbital infusion to control rse were compared with those who were controlled with continuous benzodiazepine infusion alone .
continuous data were analyzed with the mann - whitney u test , and binary data were analyzed using fisher exact test .
of 28 admissions , 4 ( 14% ) were admitted with new onset of seizures and all others had a known seizure disorder and were taking multiple antiepileptic medications .
all children in this cohort received continuous infusion of a benzodiazepine ( midazolam = 25 ; lorazepam = 4 ; both = 1 ) for seizure control .
eleven patients ( 39% ) required pentobarbital infusion in addition to benzodiazepines to control seizures while others ( 61% ) received only a benzodiazepine infusion .
the mean maximum pentobarbital infusion dosage was 5.2  1.8 mg / kg / h with a median duration of treatment of 14 ( interquartile range [ iqr ] : 12 - 76 ) days .
twenty - five patients received a continuous midazolam infusion with a mean maximum dosage of 0.41  0.43 mg / kg / h for a median duration of treatment of 4 ( iqr : 1 - 16 ) days .
only one child died who did not receive pentobarbital and the death was not related to seizure management .
demographic , resource utilization , and complications of children with refractory status epilepticus were treated with and without pentobarbital
all patients in our study received a benzodiazepine infusion as an initial anticonvulsant continuous therapy . complications and
resource utilization were less frequent in children whose seizures were controlled with only a benzodiazepine infusion .
a meta - analysis of 111 children concluded that midazolam was as effective as other coma - inducing medications and involved a lower mortality ( zero with midazolam ) , however , morrison noted that breakthrough seizure activity is common with midazolam . a standardized protocol for escalation or weaning of anti - epileptic infusion therapy was not utilized in our cohort .
pentobarbital infusion was titrated to achieve a burst suppression pattern during continuous video - eeg monitoring ; the required degree of burst suppression ( number of burst patterns per unit time ) was not standardized .
an aggressive step - wise approach to maximize benzodiazepine prior to initiating a pentobarbital infusion may have prevented some patients from requiring pentobarbital , thus limiting their complications .
developing a protocolized treatment plan similar to abend et al . may have been beneficial in limiting the side effects that we noted in our patients .
recent guidelines for the management of status epilepticus do not recommend preference to any one drug among midazolam , propofol , and pentobarbital for the management of rse . in a meta - analysis , pentobarbital treatment was associated with a lower incidence of short - term treatment failure , fewer breakthrough seizures , and decreased need for additional anti - epileptic medications , but was associated with a significantly higher frequency of hypotension as seen in our study .
studies of pentobarbital therapy for rse in children have reported an efficacy of 74 - 100% .
the loading dose of pentobarbital is generally 5 mg / kg administered over an hour , followed by an infusion at a rate of 1 mg / kg / h , which can be increased as needed to 3 mg / kg / h .
continuous blood pressure monitoring is important because hypotension may occur with dose escalation . in our cohort ,
a loading pentobarbital bolus was used inconsistently , often requiring a higher continuous dose to achieve a therapeutic effect .
our study noted two unexpected complications associated with prolonged pentobarbital treatment : movement disorders that developed during weaning or after discontinuation of pentobarbital infusion therapy and hypertension , which required medical therapy .
low mortality in our cohort may be due to lower percent of new onset rse .
however , children with a known seizure disorder presenting with rse had a low morality and their neurologic status did not worsen in spite of prolonged therapy with benzodiazepines with or without pentobarbital .
patients who required pentobarbital to control rse had a longer hospital stay with more complications .
whether aggressive escalation of midazolam therapy will reduce the use of pentobarbital and reduce complications warrants a prospective examination .
the objective of this retrospective study was to evaluate complications in the management of refractory status epilepticus ( rse ) treated with benzodiazepine and pentobarbital infusions . 
 of 28 children with rse , eleven ( 39% ) were treated with a pentobarbital infusion after failure to control rse with a benzodiazepine infusion ; while17 children ( 61% ) required only a benzodiazepine infusion . 
 the mean maximum pentobarbital infusion dosage was 5.2  1.8 mg / kg / h . twenty - five patients received a continuous midazolam infusion with an average dosage of 0.41  0.43 mg / kg / h . the median length of stay was longer for the pentobarbital group . 
 children requiring pentobarbital therapy were more likely to develop hypotension , require inotropic support , need intubation , mechanical ventilation , peripheral nutrition , and blood products ; furthermore , they were more likely to develop hypertension and movement disorder after or during weaning . in conclusion , children with rse who required pentobarbital therapy had a longer hospital stay with more complications .