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of Child Neurology

Intravenous Sodium Valproate Versus Diazepam Infusion for the Control of Refractory Status
Epilepticus in Children: A Randomized Controlled Trial
Vishal Mehta, Pratibha Singhi and Sunit Singhi
J Child Neurol 2007 22: 1191
DOI: 10.1177/0883073807306248

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Original Article
Intravenous Sodium Valproate Versus
Diazepam Infusion for the Control of
Refractory Status Epilepticus in Children:
A Randomized Controlled Trial
Vishal Mehta, MD, Pratibha Singhi, MD, FIAP, and Sunit Singhi, MD, FIAP, FAMS
An open-label, randomized controlled study was conducted at a
tertiary care teaching hospital to compare efficacy and safety of
intravenous sodium valproate versus diazepam infusion for con-
trol of refractory status epilepticus. Forty children with refrac-
tory status epilepticus were randomized to receive either
intravenous sodium valproate or diazepam infusion. Refractory
status epilepticus was controlled in 80% of the valproate and
85% of the diazepam patients. The median time to control
refractory status epilepticus was less in the valproate group
(5 minutes) than the diazepam group (17 minutes; P < .001).
None of the patients in the valproate group required ventilation
S
tatus epilepticus is a life-threatening neurological
emergency that requires immediate medical interven-
tion. It is associated with high mortality and morbid-
ity. The reported overall mortality is about 22% in adults1
and 3% to 7% in children.1,2 However, mortality in cases
with symptomatic status epilepticus is higher, and in chil-
dren it is 20%.3,4 Neurological sequelae⎯motor or cognitive
deficits⎯have been found in 9% to 28% and subsequent
epilepsy in 23% to 30% of children.5 The duration of status
epilepticus has a significant effect on the outcome.6 Timely
and effective management is thus of utmost importance in
reducing the mortality and morbidity associated with status
epilepticus.
The usual treatment of status epilepticus consists of a
bolus dose of diazepam 0.2 mg/kg, or any other benzodi-
azepine, followed by a loading dose of phenytoin 20 mg/kg
given as intravenous infusion. If seizures are still not con-
trolled, a repeat dose of phenytoin 5 to 10 mg/kg iv is given.7,8
When status epilepticus fails to respond to initial treatment
From the Department of Pediatrics, Advanced Pediatric Centre, Postgraduate
Institute of Medical Education and Research, Chandigarh, India.
Address correspondence to: Dr. Pratibha Singhi, Department of Pediatrics,
Postgraduate Institute of Medical Education and Research, Chandigarh,
160012 India; e-mail: psinghi@glide.net.in.
Mehta V, Singhi P, and Singhi S. Intravenous sodium valproate versus
diazepam infusion for the control of refractory status epilepticus in children:
a randomized controlled trial. J Child Neurol. 2007;22:1191-1197.
Downloaded from jcn.sagepub.com at HINARI NOT YET ASSIGNED on November 1, 2012
Journal of Child Neurology
Volume 22 Number 10
October 2007 1191-1197
©2007 Sage Publications
10.1177/0883073807306248
http://jcn.sagepub.com
hosted at
http://online.sagepub.com
or developed hypotension, whereas in the diazepam group 60%
required ventilation and 50% developed hypotension after start-
ing diazepam infusion. No adverse effects on liver functions
were seen with valproate. It is concluded that intravenous
sodium valproate is an effective alternative to diazepam infusion
in controlling refractory status epilepticus in children and is free
of respiratory depression and hypotension.
Keywords: refractory status epilepticus; intravenous sodium
valproate; continuous diazepam infusion
with adequate doses of benzodiazepine, phenytoin, and/or
phenobarbital infusion, it is referred to as “refractory
status epilepticus”.9,10 A number of drugs have been tried for
this serious condition including continuous infusions of
diazepam,10,11 midazolam,11,12 phenobarbital,13 thiopental,14
pentobarbital,15 propofol,16 and sodium valproate.17-25
Diazepam infusion has been found to be effective, and
because of its affordability it is often used for the treatment
of refractory status epilepticus.10 It has been found to be as
effective as midazolam infusion for the control of refractory
status epilepticus and is associated with lesser seizure recur-
rence and lesser mortality as compared with midazolam infu-
sion.11 Most of the drugs used for refractory status epilepticus
are associated with a risk of respiratory depression and
hypotension that require mechanical ventilation, vasopressor
support, and intensive care. In resource-poor countries the
high cost of this form of therapy is a limiting factor.
Use of intravenous sodium valproate has shown promis-
ing results in the management of refractory status epilepti-
cus. Preliminary studies in children18-21 and in adults22-24
have shown that sodium valproate is effective and safe over
a large range of doses as well as various rates of administra-
tion and also when given as a rapid bolus. Most of these
studies are retrospective analyses, case reports, or case
series. There is no randomized comparative study or con-
trolled trial to scientifically recommend the use of intra-
venous sodium valproate. The objective of this study was to
compare the efficacy of intravenous sodium valproate with
1191
1192 Journal of Child Neurology / Vol. 22, No. 10, October 2007
that of continuous diazepam infusion for the treatment of
refractory status epilepticus in children and also to examine
the risk of hypotension and respiratory depression that
require vasopressor and ventilatory support.
Material and Methods
The study was designed as an open-label, randomized, con-
trolled trial. Consecutive children, 5 months to 12 years of
age, with refractory convulsive status epilepticus, admitted
over a period of 1½ years to the Emergency and Neurology
wards of the Advanced Pediatric Centre, Postgraduate
Institute of Medical Education and Research, Chandigarh,
were enrolled in the study. The institute is a large, 1500-
bed, multidisciplinary tertiary care teaching and referral
hospital. It caters to the local population as well as cases
referred from neighboring states. Informed written consent
was obtained from the parents. Neonates and infants up to
3 months of age as well as known or suspected cases of
mitochondrial disorders were excluded. The study was
approved by the ethics committee of the institute.
Status epilepticus was defined as 30 minutes of continu-
ous seizure activity or 2 or more sequential seizures without
full recovery of consciousness between seizures. Patients in
whom seizures were not controlled after a bolus of diazepam
(0.2 mg/kg) followed by phenytoin (20 mg/kg in normal
saline infusion) and a repeat dose of phenytoin (5 to 10
mg/kg in normal saline infusion) 10 minutes after the first
dose were considered to have refractory status epilepticus.
Forty children with refractory status epilepticus were ran-
domized using the block randomization method to receive
either intravenous sodium valproate or diazepam infusion.
The random assignments were kept in sealed envelopes and
opened only after the child was enrolled in the study.
Sodium valproate was given as an initial loading bolus of
30 mg/kg diluted 1:1 in normal saline from 2 to 5 minutes. If
the status was not controlled within 10 minutes after the
bolus dose, a repeat bolus dose of 10 mg/kg was given. This
was followed by infusion at a rate of 5 mg/kg/hr, which was
continued until a seizure-free period of 6 hours was reached
and then reduced at a rate of 1 mg/kg/hr every 2 hours. After
discontinuation of intravenous infusion, a maintenance dose
of 10 mg/kg intravenous every 8 hours was continued until
the child could take oral anticonvulsants. If seizures were not
controlled within 30 minutes of giving intravenous sodium
valproate, this was considered a failure of valproate therapy
and diazepam was given as the next line of treatment, and if
there was no response to the maximum dose of diazepam
infusion (100 µg/kg/min) thiopental infusion was given.
In the diazepam group, the infusion was started at a rate of
10 µg/kg/min and was increased every 5 minutes by 10
µg/kg/min until status was controlled or a maximum
dose of 100 µg/kg/min was reached. The infusion was con-
tinued for at least 6 hours after control of the last seizure and
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then was gradually tapered at a rate of 10 µg/kg/min every 2
hours. If seizures were not controlled with the maximum dose
of diazepam it was considered a failure of diazepam therapy
and thiopental was then used. Thiopental was given in a load-
ing dose of 3 mg/kg followed by a continuous infusion of 0.2
mg/kg/min until the seizures were controlled.
Demographic and clinical details of the patients⎯age,
gender, weight, underlying disease, prior history of epilepsy
and treatment given, complications, and course of the
illness⎯were recorded. Vital signs, blood pressure, and oxy-
gen saturation were monitored. Endotracheal intubation
was done whenever required for airway management or res-
piratory depression as per the standard protocol of the unit.
Hypotension (blood pressure <5th percentile for age) was
treated with fluid boluses and inotropic support. Ventilation
was started if the patient was unable to maintain adequate
oxygenation on supplemental oxygen after intubation,
had irregular breathing, or an episode of apnea. The
time interval between starting the study drug and the
control of refractory status epilepticus, occurrence of
breakthrough seizures while on drug infusion, number
of breakthrough seizures, and maximum dose of drug
required to control refractory status epilepticus were
recorded. Laboratory tests including serum electrolytes,
serum bilirubin, liver enzymes, renal function, complete
blood counts, and blood sugar were measured in all the
patients before, during, and after the drug infusions.
The neurological outcome of the patients was assessed
at discharge and graded as follows: 1 = good (complete
recovery to baseline neurological function); 2 = fair (sur-
vival with some neurological sequelae requiring part time
help, care, and assistive device); and 3 = poor (death or
severe neurological sequelae requiring full-time attention
or institutionalization).
Outcome Variables
The primary outcome variables were (i) the proportion of
patients in whom status epilepticus was controlled within
30 minutes of drug administration, and (ii) the time taken
for control of status epilepticus.
If the child remained seizure-free for at least 6 hours
after control of status epilepticus, it was considered “effec-
tive control of seizures.” Control of status epilepticus was
assessed clinically and confirmed by electroencephalogra-
phy (EEG). Continuous EEG monitoring was not available.
If status epilepticus remained uncontrolled even with the
maximum dose of the study drug, it was labeled as failure of
therapy.
Secondary outcome variables included the proportion of
patients in each group who developed (i) hypotension
requiring inotropic support, (ii) respiratory depression need-
ing ventilatory support, (iii) breakthrough seizures, and (iv)
a poor neurological outcome.
 Control of Refractory Status Epilepticus / Mehta et al 1193

Table 1. Demographic and Seizure Characteristics of the Two Groupsa

Characteristics Valproate Group (n = 20) Diazepam Group (n = 20)

Age (months) mean ± SD (range) 36.3 ± 32.8 (7-120) 44.5 ± 42.8 (5-144)
Median 27 27
Gender ratio (boys:girls) 14:6 17:3
Known case of epilepsy 6 2
Type of seizure
Generalised tonic-clonic 9 (45%) 9 (45%)
Focal with secondary generalization 7 (35%) 5 (25%)
Simple partial 3 (15%) 5 (25%)
Multifocal 1 (5%) 1 (5%)
Duration of status epilepticus before admission (minutes)
Median 30 30
Range (10th to 90th percentile) (5.5-147) (10-441)
Treatment for present episode of seizure before admission 13 (65%) 14 (70%)

a. P > .1 in all.

Table 2. Etiology of Refractory Status Epilepticus in the Status Epilepticus Control

Two Groupsa
Details of status epilepticus control are shown in Table 3.
Valproate Group Diazepam Group Refractory status epilepticus was successfully controlled
Etiology (n = 20) (n = 20) within 30 minutes in 80% of children in the sodium val-
Meningoencephalitis 9 (45%) 11 (55%) proate group and 85% in the diazepam group (P value not
Pyogenic meningitis 1 (5%) 3 (15%) significant). Control of refractory status epilepticus could
Central nervous system 1 (5%) 1 (5%) be achieved in all the children in the diazepam group by fur-
tuberculosis ther increasing the rate of diazepam infusion (maximum up
Epilepsy 3 (15%) 1 (5%)
to 100 µg/kg/min). Four children in the valproate group, in
Intracranial bleeding 2 (10%) 1 (5%)
Metabolic disorderb 1 (5%) 1 (5%) whom status epilepticus was not controlled within 30 min-
Others 3 (15%)c 2 (10%)d utes, were given diazepam infusion. Status epilepticus was
controlled in 3 of them whereas 1 patient required thiopen-
a. P > .1. Intracranial bleeding includes 2 cases of head trauma and 1 case of
late onset hemorrhagic disease of the newborn (LHDN).
tal infusion. Time taken for control of refractory status
b. Biotinidase deficiency. epilepticus after drug administration was significantly less
c. One case each of dapsone poisoning, mesial temporal sclerosis, and uremic in the valproate group as compared to the diazepam group
encephalopathy (HUS).
d. Acute disseminated encephalomyelitis (ADEM).
(P = .001).
Mean dose of sodium valproate required for control of
refractory status epilepticus was 37.5 ± 4.4 mg/kg (median
Statistical Analysis 40 mg/kg). Five patients responded to the initial loading
dose of 30 mg/kg, whereas others needed a second bolus of
Data between the 2 groups was analyzed using chi-square 10 mg/kg to control refractory status epilepticus. All of them
test or Fisher’s exact test to compare the proportions and received continuous infusion of 5 mg/kg/hr after initial con-
two-tailed student t-test, paired t-test, or Mann Whitney trol of status epilepticus. In the diazepam group, the mean
U test for continuous data. P values <0.05 were consid- maximum dose required for control of refractory status
ered significant. Continuous variables were expressed as epilepticus was 44 ± 24.1 µg/kg/min (median 35 µg/kg/min).
mean ± 2 SD. Breakthrough seizures while on drug infusion occurred
in a similar number of children in both groups. The 2 major
groups of patients in whom status was not controlled within
Results 30 minutes were (a) meningoencephalitis cases, who pre-
sented late to the hospital and had a longer duration of
Twenty children each were randomized to the sodium val- seizures before admission; and (b) children with intractable
proate and diazepam groups. Both groups were comparable epilepsy on polytherapy.
with respect to age, gender, etiology of status epilepticus,
type of seizures, and antiepileptic treatment received before
Respiratory Depression and Ventilation
admission (Table 1). The most common cause of status
Requirement
epilepticus was central nervous system infection (Table 2).
In the majority of cases, status epilepticus was the first Three children in the valproate group and 1 child in the
episodes of seizures; only 20% were known cases of epilepsy diazepam group needed ventilation before administration of
on anticonvulsant treatment. the study drug. None of the children in the valproate group

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1194 Journal of Child Neurology / Vol. 22, No. 10, October 2007

Table 3. Comparison of the Two Groups With Respect to Refractory Status Epilepticus Control and Adverse Effectsa

Status Control Variables Valproate Group (n = 20) Diazepam Group (n = 20) P value

RSE controlled within 30 minutes 16 (80%) 17 (85%) 1.0

Time interval for control of RSE after giving study drug (minutes)
Mean ± SD 8.8 ± 7.4 26.6 ± 26.7 .001
Median 5 17
Range (5th to 95th percentile) 2-25 5-117
Dose of drugs required to control RSE
Mean ± SD 37.5 ± 4.44 44 ± 24.1
Median 40 35
Range (5th to 95th percentile) 30-40 mg/kg 10-80 µg/kg/min
Breakthrough seizures 8 (50%) 8 (40%) .73
Respiratory depression after drug administration 0 12 (60%)
Hypotension after drug administration 0 10 (50%)

NOTE: RSE = refractory status epilepticus; SD = standard deviation

a. All values are number of patients and (%).

developed respiratory depression or required ventilation Table 4. Comparisons of Outcome of the Patients
after valproate administration, whereas in the diazepam of the Two Groups
group 12 (60%) children developed respiratory depression
Valproate Diazepam
and required ventilation after starting diazepam infusion Group Group Total
(P < .01). Mean dose of diazepam infusion at which poor Outcome (n = 20) (n = 20) (n = 40) P value
respiratory effort occurred was 32.5 ± 7.5 µg/kg/min, and
Good 5 (25%) 6 (30%) 11 (27.5%) .93
median was 30 µg/kg/min.
Fair 11 (55%) 10 (50%) 21 (52.5%)
Poor 4 (20%) 4 (20%) 8 (20%)
Hypotension and Inotropic Support
None of the children in the valproate group developed
hypotension after valproate administration, whereas 50% pressure and 1 each had uremic encephalopathy and
(10 out of 20) of the children in the diazepam group devel- intractable epilepsy.
oped hypotension and 40% (8 out of 20) required vasopres-
sor support after starting diazepam infusion (P < .01). Of
the 4 children in whom status epilepticus was not con- Discussion
trolled with sodium valproate and who received diazepam
infusion as the next drug, 3 developed hypotension and Our study has shown that intravenous sodium valproate is
required inotropic support after starting diazepam infusion. an effective and safe therapy for the control of refractory
status epilepticus. This is consistent with published experi-
mental and clinical data. Honack et al,17 in a mouse model
Admissions to Pediatric Intensive Care Unit
of status epilepticus, showed that intravenous valproic acid
A total of 30 out of 40 children were admitted to the pedi- has a rapid anticonvulsant activity and achieves high drug
atric intensive care unit for various indications including levels in the brain due to good central nervous system pen-
raised intra cranial pressure in 45%, uncontrolled status etration. There was no lag time between peak serum and
epilepticus or status related complications in 30%, septic peak brain concentrations. Several studies in human beings
shock in 10%, and pneumonia in 7%. Significantly more have reported similar early control of seizures, indicating
children in the diazepam group (95%) as compared to the that sodium valproate has some immediate antiepileptic
sodium valproate group (55%) (P = .008) needed pediatric effect and is capable of rapidly stopping seizure activity in
intensive care unit admission. patients with refractory status epilepticus.18
We compared the use of intravenous sodium valproate
Outcome with diazepam infusion, which is the current drug of choice
for the management of refractory status epilepticus in our
Survival and neurological outcome were similar in both institute. In a previous study, diazepam infusion was found
groups (Table 4). Most of the patients (52.5%) had a fair out- to be better than midazolam infusion in our patients.11
come, 33 (82.5%) patients survived, and 7 patients died (4 However, the use of diazepam infusion was associated with
on valproate and 3 on diazepam). Among the patients who respiratory depression and hypotension in about half the
died, 5 had meningoencephalitis with raised intracranial cases. We found intravenous valproate to be as effective as

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diazepam infusion for the control of refractory status epilep-
ticus. More than 80% of children had control of seizures
within 30 minutes in both groups. This is similar to pub-
lished data on the use of intravenous valproate in childhood
status epilepticus. Control of refractory status epilepticus
with intravenous valproate was reported in 78% (32 of 41)
of children by Uberall et al19 and in 100% (18 of 18) of chil-
dren by Yu et al.20 However, in the study by Campistol
et al,21 control of status epilepticus with intravenous sodium
valproate was seen in only 58% (11 of 19) of the children.
All 3 studies were retrospective and used different doses
and regimes of drug administration. Uberall et al used a
dose of sodium valproate, which was similar to that used by
us, and found it effective in 78% of children, which is sim-
ilar to our results. Campistol et al21 used a smaller dose of
sodium valproate (20 mg/kg loading followed by 1 mg/kg/hr
infusion) and reported a lower rate of success (58%) in con-
trolling refractory status epilepticus. In adults, control of
refractory status epilepticus with intravenous sodium val-
proate has been varyingly reported in 63% to 91% of
cases.22-24
The efficacy of diazepam infusion in this study was
similar to that reported in a previous study from our insti-
tution.11 Three patients in the diazepam group in whom
status epilepticus was not controlled within 30 minutes of
starting infusion responded to a further increase in the
rate of diazepam infusion. Thus, diazepam was effective
in controlling seizures in all the cases. On the other hand,
4 patients in the sodium valproate group in whom status
epilepticus was not controlled within 30 minutes of giv-
ing a maximum valproate dose of 40 mg/kg had to be
given diazepam infusion as per protocol. It is, however,
possible that a further increase in the dose of valproate
might have controlled status epilepticus.
Time taken for control of refractory status epilepticus
after drug administration was significantly less in the val-
proate group (median 5 minutes) as compared to the
diazepam group (median 17 minutes) (P = .001). In the val-
proate group, results were similar to those in studies by
Uberall et al19 (2 to 6 minutes) and Yu et al20 (8 minutes).
In the diazepam group, results were similar to those in stud-
ies of diazepam infusion by Singhi et al11 (16 minutes). The
faster control of refractory status epilepticus in the sodium
valproate group was probably due to the differences in drug
administration protocols used in the 2 groups. Valproate
was used as an initial bolus to achieve therapeutic or
supratherapeutic drug levels for control of status epilepticus
followed by a continuous infusion to maintain those levels.
On the other hand, diazepam was started at a minimum
dose and stepped up gradually to achieve a desired clinical
action and to avoid undesired adverse effects.
An added reason for late control of refractory status
epilepticus in the diazepam group could be a more severe
refractory status epilepticus in this group, although median
duration of seizures prior to admission was similar in both
groups. There were 4 patients in the diazepam group who
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Control of Refractory Status Epilepticus / Mehta et al 1195
presented very late with seizure duration more than 300
minutes prior to admission, whereas in the valproate group
the maximum seizure duration before admission was 180
minutes.
The mean dose of sodium valproate (37.5 mg/kg)
required for control of refractory status epilepticus in this
study was comparable to that reported by Uberall et al19
(33.1 mg), but higher than that reported by Yu et al20 (25
mg/kg). Mean infusion rate of diazepam required to control
refractory status epilepticus (44 ± 24.1 µg/kg/min) was also
slightly higher in the present study as compared to previous
studies from our institute (30 ± 20 µg/kg/min).11
The number of patients who developed breakthrough
seizures while on drug infusion was similar in the 2 groups
(P = .73). A majority of the patients (75%) who received
sodium valproate required a repeat bolus of 10 mg/kg fol-
lowing the initial loading dose of 30 mg/kg for control of
refractory status epilepticus. In the study by Uberall et al,
only 5 of 41 patients required a second bolus dose of
sodium valproate.19 However, the initial loading dose of
sodium valproate in their study was not uniform and ranged
between 20 and 40 mg/kg. Also, on further analysis they
found that patients who received an initial loading bolus
dose between 30 and 40 mg/kg had better control of status
epilepticus as compared to those who received a dose
between 20 and 30 mg/kg.19 This suggests that the use of a
higher initial loading dose (about 40 mg/kg) might be asso-
ciated with better control of seizures and with a smaller
number of breakthrough seizures.
None of the patients in the valproate group required
ventilation or developed hypotension after valproate admin-
istration. In contrast, 60% of patients in the diazepam group
required ventilation, 50% developed hypotension, and 40%
of them needed vasopressor support after starting diazepam
infusion. Previous studies on the use of intravenous sodium
valproate have also not reported any respiratory depression
or hypotension after its use.19-25
The use of valproate is generally associated with a fear of
hepatotoxicity and thrombocytopenia. However, none of our
patients had evidence of hepatotoxicity or thrombocytope-
nia after valproate administration. Our findings were simi-
lar to those from previous studies in which the safety of
rapid intravenous sodium valproate was evaluated and no
significant hematological or liver function abnormality was
found.25,26 Mild hematological abnormalities have been
reported in 1% to 32% of patients receiving oral sodium val-
proate; however, the risk of developing severe thrombocy-
topenia or bleeding complications is very low.27 No serious
haemostatic adverse effects were seen in traumatic brain
injury patients who were receiving valproate.28 In our study
of 40 children, 3 had intracranial bleeding (in 2 this was a
post head injury and in 1 it was because of late onset hem-
orrhagic disease of the newborn). All of them had bleeding
before the start of anticonvulsant therapy.
Admission to the pediatric intensive care unit was
required in a smaller number of children in the valproate
1196 Journal of Child Neurology / Vol. 22, No. 10, October 2007
group (55%) as compared to the diazepam group (95%) (P =
.008). This was most likely due to a higher incidence of
respiratory depression requiring ventilation and from
hypotension requiring inotropic support as well as the need
for cardiorespiratory monitoring in the diazepam group.
However, underlying disease, associated complications, and
presence of raised intracranial pressure were other impor-
tant determinants for pediatric intensive care unit admis-
sions. These findings could not be compared with previous
studies of refractory status epilepticus done at our institute
and with others because all the patients in these studies were
admitted in the pediatric intensive care unit. The number of
patients requiring ventilation after receiving diazepam infu-
sion was slightly higher in the present study as compared to
a previous study (47%) from our institute.11 This could pos-
sibly be due to inclusion of children with a greater severity of
refractory status epilepticus, particularly in the diazepam
group, in which 4 patients had seizures for more than 300
minutes before admission.
Mortality in patients with refractory status epilepticus
was somewhat lower (17.5%) in the present study as com-
pared to a previous study (25%) of refractory status epilep-
ticus done in our institute.8 Various other studies using
different treatment modalities have reported a variable mor-
tality in refractory status epilepticus patients ranging from
20% to 48%.4,13-16 In the present study neurological outcome
was fair in about half the patients and good in about a quar-
ter. This was comparable in both the valproate and the
diazepam groups (P = .93) and was also similar to previous
studies in which midazolam and diazepam infusion were
used.10,11 Therefore, outcome seems to be strongly related to
the etiology rather than to the treatment given for control of
refractory status epilepticus.
Valproate is generally avoided in children under the age
of 2 years because of a fear of a high risk of hepatotoxicity,
especially in children on phenobarbitone or polytherapy.
Caution is also advised on the use of valproate in children
with an underlying liver disease or a suspected metabolic
disorder such as mitochondrial disorder. Previous studies on
the use of intravenous sodium valproate in children with
refractory status have included children less than 2 years of
age and have found intravenous sodium valproate safe and
effective.19-21 However, those results could be because of
smaller number of children involved in the studies. In the
present study, children between 3 months and 12 years of
age were enrolled and none of them had significant hepatic
or hematological dysfunction. Thus, intravenous sodium
valproate is found to be safe; however, the standard cautions
for its use must be observed.
Conclusion
We conclude that intravenous sodium valproate is as effec-
tive as diazepam infusion for the treatment of refractory
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status epilepticus in children and is free of adverse effects,
such as respiratory depression and hypotension, which are
often associated with benzodiazepine infusion. Moreover,
the use of valproate is associated with a decreased need for
ventilation, inotropic support, and intensive care admis-
sions. Hence, intravenous sodium valproate seems to be a
good first-choice drug for the management of status epilep-
ticus refractory to adequate doses of diazepam and pheny-
toin. Perhaps a new protocol can be suggested for the
management of refractory status epilepticus in which the
use of intravenous sodium valproate is positioned before
the use of benzodiazepine infusion.
References
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