4. Question : Does IM
Benzodiazepine as effective
as IV for pre-hospital seizure
cessation
in status epilepticus patient ?
Pre-hospital status epilepticus
Patient patient
Intervention IM Benzodiazepine
Comparison IV Benzodiazepine
5. SEARCH
Date 28 2555
Search engine: PubMed
Intramuscular versus Intravenous for Prehospital
Search term: Status Epilepticus
Systematic review
0
results
Number of search
5
result
Number of search
3
results Limit
Relevant most
2
results
Intramuscular versus Intravenous Therapy for
Prehospital Status Epilepticus
double-blind, randomize controlled trials
, noninferiority trial
6.
7. Key Message
Early termination of prolonged epileptic
seizures in response to intravenous
administration of benzodiazepines by
paramedics in the prehospital setting is
associated with better patient outcomes.
8. Introduction
Many emergency medical services
This practice has become
(EMS) systems, however, have
increasingly common despite the
begun to use IM midazolam rather
lack of clinical-trial data regarding
than an IV agent, largely because IM
the efficacy and safety of
administration is faster and is
intramuscular midazolam.
consistently achievable.
We therefore performed a noninferiority
study to determine whether IM
midazolam is as effective as IV
lorazepam, with a similar degree of
safety, for terminating status epilepticusdirectors need a
Although IV lorazepam is the EMS medical
preferred treatment , it is rarely practical alternative that is at
seizures before arrival at the hospital.
used by paramedics in the least as safe and effective as
prehospital setting IV lorazepam.
9. Method : Study Design
The Rapid
Anticonvulsant The trial was
Medication Prior to performed under an
Arrival Trial (RAMPART) Investigational New
was a randomized, Drug application with
double- blind, phase 3, the Food and Drug
noninferiority clinical Administration (FDA)
trial
10. Method : Study Subjects
The intended study population included children with an estimated
body weight of 13 kg or more and adults requiring treatment with
benzodiazepines for statusepilepticus in the prehospital setting.
Subjects were enrolled Subjects were excluded for the
if they were having convulsive seizures following reasons
at the time of treatment by paramedics • the acute precipitant of the seizures was major
trauma
and were reported by reliable
• Hypoglycemia
witnesses to have been continuously • cardiac arrest, or a heart rate of less than 40 beats
convulsing for longer than 5 minutes or per minute (since these conditions require
if they were having convulsive seizures alternative treatments)
at the time of treatment after having • they had a known allergy to midazolam or
lorazepam
intermittent seizures without regaining • they were known to be pregnant or a prisoner
consciousness for longer than 5 • they were being treated as part of an other study;
minutes. or, preemptively
• they opted out of this study by wearing a medical-
alert tag marked “RAMPART declined.”
11. Results
intramuscular- intravenous-
RESULTS
midazolam group lorazepam group
seizures were absent without rescue 329 of 448 subjects
282 of 445 (63.4%)
therapy (73.4%)
need for endotracheal intubation 14.1% of subjects 14.4% of subjects
recurrence of seizures 11.4% of subjects 10.6% of subjects
median times to active treatment 1.2 minutes 4.8 minutes
median times from active treatment to
3.3 minutes 1.6 minutes
cessation of convulsions
Adverse-event rates same
absolute difference, 10 percentage points; 95% confidence interval 4.0 to 16.1;
P<0.001 for both noninferiority and superiority
12.
13.
14. Conclusions
For subjects in
status epilepticus,
intramuscular
midazolam is at least
as safe and effective
as intravenous
lorazepam for
prehospital seizure
cessation.
15. CRITICAL APPRAISAL
WORKSHEET FOR
THERAPY
Intramuscular versus Intravenous Therapy for
Study citation :
Prehospital Status Epilepticus
Method of study : double-blind, randomized, noninferiority trial
16. opening an Each kit contained
For subjects
instrumented box two color-coded,
who met the
containing a study shrink-wrapped
eligibility criteria
drug kit. study- drug bundles,
one intramuscular Blinding and simple randomization with equal
autoinjector and one numbers of subjects assigned to the two study
prefilled intravenous groups were achieved with the use of a double-
syringe dummy strategy
All subjects were treated with the Subjects were considered to be
intramuscular autoinjector, after which enrolled in the trial when the
intramuscular auto- injector was
venous access was immediately achieved applied, regardless of whether the
and treatment was administered by means intramuscular dose was
of intravenous syringe. successfully delivered.
All adults and those children with an estimated body weight of more than 40 kg received either 10 mg of intramuscular midazolam followed
by intravenous placebo or intramuscular placebo followed by 4 mg of intravenous lorazepam. In children with an estimated weight of 13 to 40
kg, the active treatment was 5 mg of intramuscular midazolam or 2 mg of intravenous lorazepam.
17. A voice recorder Paramedics were instructed to record oral statements when
intramuscular treatment was administered, when
was activated by
intravenous access was obtained, when the intravenous
opening the study study drug was administered, when any rescue treatments
box. were given, and when convulsions were observed to stop.
Each statement
Paramedics also stated whether the
was time-stamped
subject was convulsing on arrival at
by the study box’s
the emergency department.
internal clock.
When it was difficult to obtain intravenous access, If convulsions resumed later
paramedics were instructed to continue attempts during EMS transport,
for at least 10 minutes, but they were permitted to rescue therapy (according
use intraosseous access at any time in lieu of to the local protocol) was to
intravenous access. be given.
Rescue therapy, as dictated by local EMS protocol, was recommended for use in subjects
who were still convulsing 10 minutes after the last study medication was administered
18. Are the results of this single preventive or
therapeutic trial valid?
Items Yes/No Note
1. Was the assignment of patients to treatments Yes
randomized?
2. Was the randomization is concealed? Yes
3. Were all patients analyzed in the groups to which Yes
they were randomized (intention- to-treat)?
4. Were patients and clinicians kept “blind” to their
Yes
treatment?
5. Were the groups treated equally, apart from the
Yes
experimental treatment (co-intervention)?
6. Were all patients who entered the trial accounted
Yes
for at its conclusion (follow up complete)?
19. Can you apply this valid, important evidence about
therapy in caring for your patient?
Items Yes/No Note
1. Is your patient so different from those in the study
No
that its results cannot apply?
2. Is the treatment feasible in your setting? No
3. Is your patient met by this regimen and its
Yes
consequences on benefit and harm?
4. Do your patient and you have a clear assessment of
No
their values and preferences?
3 Although IV lorazepam is the preferred treatment for patients with seizures in the emergency department (and was the most effective treatment in the PHTSE trial), it is rarely used by paramedics in the prehospital setting because of the potential difficulty with IV administration, as well as the short shelf-life of lorazepam when it is not refrigerated.
, in which each kit was randomly assigned at the central pharmacy to contain either the active intramuscular drug with intravenous placebo or intramuscular placebo with the active intravenous drug.
For the purposes of this trial, intraosseous access to the vascular space was considered equivalent to intravenous access.. If there was a delay in obtaining intravenous access and the subject stopped having seizures before the intravenous study drug could be given, the intravenous study medication was not used.
