article282

RAMPART

"Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus". The New England Journal of Medicine. 2012. 366:591-600. PubMed • Full text • PDF

1. Clinical Question
2. Bottom Line
3. Major Points
4. Guidelines
5. Design
6. Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7. Interventions
8. Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9. Criticisms
10. Funding
11. Further Reading

Clinical Question

In children and adults in status epilepticus treated by paramedics, is intramuscular midazolam as safe and effective as intravenous lorazepam?

Bottom Line

Intramuscular midazolam is at least as safe and effective as intravenous lorazepam for prehospital seizure cessation and might be superior in terminating seizures before hospital arrival in patients with status epilepticus treated by paramedics.

Major Points

Guidelines

At the time of publication, no guidelines were provided within the article.

Design

- Multicenter, double-blind, parallel group, randomized, placebo-controlled noninferiority trial.
- N=893 subjects (with a total of 1023 enrollments, reenrollment rate 13%).
- Intramuscular midazolam (n=448) vs. Intravenous lorazepam (n=445).
- Setting: 33 EMS agencies, 79 receiving hospitals across the United States.
- Enrollment: June 15, 2009 to January 14, 2011.
- Follow-up at hospital discharge or 30 days after enrollment.
- Intention-to-treat analysis.

Population

Inclusion Criteria

- Children with an estimated body weight of ≥13 kg and adults requiring benzodiazepines for status epilepticus in prehospital setting.
- Continuous convulsions for >5 minutes or having convulsive seizures after intermittent seizures without regaining consciousness for >5 minutes.

Exclusion Criteria

- Acute precipitant of seizures: major trauma, hypoglycemia, cardiac arrest, heart rate of <40 bpm.
- Known allergies to midazolam or lorazepam.
- Known pregnancy or prisoner status.
- Participation in another study.

Baseline Characteristics

- Balanced groups regarding demographic and clinical characteristics.
- History of epilepsy, diagnosis of status epilepticus, and underlying cause analysis.

Interventions

- Intramuscular midazolam autoinjector followed by intravenous placebo, or
- Intramuscular placebo followed by intravenous lorazepam.

Outcomes

Primary Outcome

- Absence of seizures upon arrival in the emergency department without the need for rescue therapy: 73.4% in the intramuscular midazolam group vs. 63.4% in the intravenous lorazepam group (absolute difference, 10 percentage points; 95% CI, 4.0 to 16.1; P<0.001 for noninferiority and superiority).

Secondary Outcomes

- Need for endotracheal intubation: 14.1% with intramuscular midazolam vs. 14.4% with intravenous lorazepam.
- Recurrence of seizures: 11.4% with intramuscular midazolam vs. 10.6% with intravenous lorazepam.
- Median times to active treatment and cessation of convulsions: Faster with intramuscular route than intravenous.
- Adverse-event rates similar in the two groups.

Criticisms

- The importance of using an autoinjector for intramuscular injections, as compared with conventional intramuscular injections, is not determined.
- The study was not designed to separate the effect of the agent from the route of administration.
- No placebo control group; however, including one would have been unethical due to established benefit of benzodiazepines over no treatment.

Funding

- National Institute of Neurological Disorders and Stroke, National Institutes of Health Office of the Director CounterACT Program, and Biomedical Advanced Research and Development Authority of the Assistant Secretary for Preparedness and Response.
- Autoinjectors provided through a cooperative agreement with the National Institute of Neurological Disorders and Stroke by the Department of Defense.