VOLUME 40 : NUMBER 1 : FEBRUARY 2017

ARTICLE

Midazolam for status epilepticus

Rob Smith
SUMMARY Paediatric neurologist1
Conjoint senior lecturer2
Midazolam is now the first-line treatment for status epilepticus in children.
Janis Brown
The drug can be given via several different routes. Transmucosal administration is safe, effective, Clinical nurse consultant
easier to use and more socially acceptable than rectal diazepam. epilepsy1

The aim is to stop convulsive seizures that have lasted longer than five minutes as soon as possible.
1
John Hunter Children’s
Hospital
Transmucosal pre-hospital administration by carers is recommended for patients with a Newcastle
predilection for prolonged seizures, or those with limited access to emergency services. This 2
Faculty of Health and
reduces the time to treat and improves outcomes. Medicine
University of Newcastle
General practitioners can obtain midazolam through the Prescriber Bag Drug Supplies section New South Wales
of the Pharmaceutical Benefits Scheme. For pre-hospital use, 5 mg in 1 mL plastic ampoules
is recommended. Keywords
Doctor's Bag, emergency
drugs, midazolam,
Introduction First-line drugs Pharmaceutical Benefits
Midazolam is a benzodiazepine which has been For many years, intravenous or rectal diazepam was Scheme, status epilepticus
used in the treatment of status epilepticus the first-choice drug for stopping status epilepticus.
since the early 1990s. Midazolam has replaced It is effective but can be difficult to use, and Aust Prescr 2017;40:23–5
diazepam as the preferred first-line drug for acute rectal administration was less socially acceptable
http://dx.doi.org/10.18773/
management of seizures in infants and children. outside hospital. austprescr.2017.005
It is not currently registered for this indication Midazolam is a water-soluble benzodiazepine which
in Australia, but in 2015 midazolam was made can be given intramuscularly, intravenously or
available for emergency use by GPs through the transmucosally. It was incorporated into a guideline
Pharmaceutical Benefits Scheme and is widely used for the management of seizures published by
off label for the treatment of seizures. Midazolam the New South Wales (NSW) Ministry of Health
may also be administered by parents and carers at in 2009.3 The 2016 version of this guideline says
home and school, by ambulance officers and in the that midazolam is the drug of first choice when
emergency department. intravenous access has not been obtained.4
Administering midazolam outside hospital reduces
Treating status epilepticus
the time-to-treat period and improves outcomes.5
Most convulsive seizures do not last longer
Midazolam can also be used to terminate clusters of
than five minutes and resolve without medical
brief convulsive seizures and manage bouts of non-
intervention. Any convulsive seizure lasting longer
convulsive status epilepticus.
than five minutes should be treated as there is an
increased risk of neuronal compromise following Second-line drugs
prolonged seizures.1 Established second-line drugs include phenytoin,
Drugs, such as midazolam, are used to abort phenobarbitone and levetiracetam. These are given
ongoing seizures and thereby avoid the after transfer to an emergency facility if first-line
complications of prolonged status epilepticus. drugs fail to stop the seizures.
The drugs resolve the majority of emergency
Emergency use of midazolam
presentations and they work best if given soon
after the seizure has exceeded five minutes. Drug The aims of giving midazolam are to avoid
treatment becomes less effective if the seizure progression to, and the complications of, convulsive
lasts longer than 15 minutes.2 Repeat doses may be status epilepticus. Early treatment improves outcomes
effective but increase the risk of complications and and avoids complications.
sometimes inappropriately delay administration of Plastic ampoules of 5 mg in 1 mL (containing
second-line therapy. approximately 18 drops) are easier to use than the

Full text free online at nps.org.au/australianprescriber 23

 VOLUME 40 : NUMBER 1 : FEBRUARY 2017

ARTICLE Midazolam for status epilepticus

Fig. 1 Technique for administering Fig. 2 Technique for administering

buccal midazolam intranasal midazolam

Reproduced with permission. The Royal Children’s

Hospital, Melbourne, Australia; Kids Health Info;
www.rch.org.au/kidsinfo

Reproduced with permission. The Royal Children’s

glass ampoules. They should be protected from light, Hospital, Melbourne, Australia; Kids Health Info;
www.rch.org.au/kidsinfo
kept in their foil wrapper until required and stored at
15–25° C.
Current guidelines recommend an initial buccal
or intranasal dose of 0.3 mg/kg to a maximum of be arranged through patient support organisations
10 mg.4 Each drop of the 5 mg/mL solution contains such as Epilepsy Action (www.epilepsy.org.au) and
approximately 0.3 mg midazolam. Absorption takes Epilepsy Australia (www.epilepsyaustralia.net).
approximately 1–3 minutes and midazolam can take Prepare clear concise directions for administration.
up to 10 minutes to abort the seizure. The dose can A suitable administration template can be found on
be repeated after five minutes if seizures persist. the Paediatric Epilepsy Network NSW website.8
The techniques for administration are described
Safety and tolerability
on the websites of the Royal Children’s Hospital
The common adverse effects of transmucosal
Melbourne6,7 and the Paediatric Epilepsy Network
midazolam are sedation, ataxia, irritability or
NSW8 (see Figs 1 and 2).
euphoria, and mild respiratory depression. Intranasal
Ambulance officers and paramedics in NSW
administration may also produce local irritation,
use midazolam in single or repeated doses of
stinging, sometimes with eyes watering and a
0.15 mg/kg intramuscularly or intravenously for
runny nose.
children in convulsive status epilepticus. They can
Avoid using the intranasal route in children with
give adults cumulative 2.5–5 mg intravenous doses
any awareness during seizures because of the
of up to 15 mg in total.9 Emergency departments
irritation. We recommend using a reusable mucosal
follow the relevant state guidelines for children and
atomisation device for intranasal administration,
adults with midazolam as the first-choice therapy.3,10
delivering half the dose into each nostril. Mucosal
Administration by carers atomisation devices may be available through
When used in the community midazolam can reduce hospitals or the ambulance service and can be
hospital admissions for children with complex purchased privately.
epilepsy.11 Providing a supply of midazolam to a Major complications of treatment are unlikely when
parent or carer can be considered for children (and the guidelines for midazolam are followed.12 With a
dependent adults) who have convulsive seizures single dose, respiratory depression is rare. Cumulative
which frequently last more than five minutes. subsequent doses are much safer if given where
Parents and carers can be anxious about giving expert airway support is available.
midazolam so training is needed. Education is When midazolam is provided for use by carers,
available from specialist epilepsy nurses and can we recommend nominating only one prescriber

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VOLUME 40 : NUMBER 1 : FEBRUARY 2017

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and one dispenser for each child in order to avoid •• blocked noses
confusion. This is most often the treating neurologist •• confusion between ‘mL’ and ‘mg’ and the risk of
and the hospital pharmacy because of the restricted accidental overdosing
availability of the plastic ampoules. Midazolam is
•• failure to adjust doses for growing children.
available in a range of concentrations and volumes
so we restrict prescription to 5 mg in 1 mL plastic
ampoules, wherever possible, to avoid dosing errors. Conclusion
Having a single prescriber and dispenser also reduces
the potential for abuse and stockpiling. In a review of Midazolam is a benzodiazepine which is now the
four years of pre-hospital use we found only two out recommended first-line drug for treating convulsive
of 197 families with circumstantial evidence of carers status epilepticus. When used according to
abusing the drug.13 guidelines for infants, children and adults it appears
safe and effective.
Parents used to using plastic ampoules may struggle
without extra instruction if glass ampoules are The use of midazolam by carers in the community is
dispensed. It is always best to review parental a widely accepted but off-label practice. It must be
understanding and techniques periodically. Frequent carefully planned, supervised and controlled.
problems include:
Conflict of interest: none declared
•• loss of dose from ‘salivary washout’ in dribbly
children
•• dose swallowing in partially aware children

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