1. Department of Pharmacy, Texas Children’s Hospital, Houston, TX3
Higher Yield Studies in a Pediatric Epilepsy Monitoring Unit: Intravenous Midazolam Versus Intravenous Lorazepam as First Line Therapy for Status Epilepticus
Kelly Frost, CPNP
Kelly Frost2, Mindl Messinger1,3, Laura Whittaker2, Sunita N. Misra2, Teri Baierlipp2, Mallory Fernandez2, Jessica Frontiero2, Dean Johnson2, Rohini Coorg1, Anne Anderson1
Department of Pediatric Neurology and Neurophysiology, Baylor College of Medicine, Houston, TX1,
Department of Pediatric Neurology and Neurophysiology, Texas Children’s Hospital, Houston, TX2,
Department of Pharmacy, Texas Children’s Hospital, Houston, TX3

2. Objectives Define status epilepticus
Explain the differences between IV midazolam (MDZ) and IV lorazepam (LZP) in terms of storage, preparation for administration, and dosage form.
Compare the pharmacodynamics of IV MDZ versus IV LZP.
Discuss whether IV MDZ or IV LZP was administered more efficiently and which was more effective in stopping status epilepticus (SE) in a shorter amount of time.
Explain the long-term benefits of this study.

3. Background
Types of patients in the EMU- spell characterizations, poorly controlled epilepsy with worsening seizures, surgical evaluations, invasive monitoring
Most of our patients are in the EMU to have seizures.
All patients have a seizure rescue plan in place, with appropriate abortive agents ordered for prn use.
If the patient is considered to be high-risk for status epilepticus (prior history of SE or active weaning of antiepileptic drugs or AEDs), they will typically have a PIV and orders for IV rescue medication.

4. Rationale
Per evidence based guidelines, LZP 0.1 mg/kg (max: 4 mg) IV was first line therapy for SE prior to this study.
However, delays in administration occurred due to required refrigeration and dilution.
MDZ does not require refrigeration or dilution and is routinely used in the field for SE (IM administration).
MDZ has a shorter half-life than LZP, thus a shorter duration of action and quicker patient recovery time, which could facilitate the recording of more seizures.
Last year, a pilot trial of IV MDZ was implemented as first line therapy for SE in the same pediatric EMU. It was shown to be administered in a reasonable and safe amount of time for SE.

5. Rationale Midazolam IV Lorazepam IV Storage
Store at 20 to 25 degreesC, 68 to 77 degreesF
Refrigerated, protect from light
Preparation for administration
No dilution required
Dilute IV dose prior to use with an equal volume of compatible diluent (D5W, NS, SWFI)
Dosage form
2 mg/2 mL, 5 mg/5 mL
2 mg/mL; 4 mg/mL
Pharmacodynamics
Onset of action: 3 to 5 minutes
Half-life elimination: 2.9 to 4.5 hours
Onset of action: within 10 minutes
Half-life elimination: 15.8 to 17.8 hours

6. Objective
The primary objective was to decrease the time from drug administration to start of next seizure in order to facilitate higher yield EMU studies.

7. Methods
Single center, prospective (MDZ data)/retrospective (LZP data) cohort study at Texas Children’s Hospital between July 2012 – July 2017
Indications for drug administration were SE (clinical and subclinical) and seizure clusters
SE defined as a seizure lasting ≥5 minutes
Seizure cluster defined as ≥3 seizures within 30 minutes
Data collected:
Demographics, dosing information, side effects
Time from seizure start to drug administration
Time from drug administration to next seizure
Data compared between IV MDZ and IV LZP

8. Methods For data analysis only included patients in SE
The midazolam dose administered was 0.2 mg/kg (max 5 mg/dose) slow IV push every 3 minutes as needed for up to 2 doses.
The lorazepam dose administered was 0.1 mg/kg (max 4 mg/dose) slow IV push every 5 minutes as needed for up to 2 doses.
The primary endpoint was defined as the time from drug administration to start of next seizure.

9. Results Figure 1. Number of patients meeting inclusion criteria
MDZ
N = 23
8 for SE
LZP
N = 62
16 for SE
Table 1. Demographics
MIDAZOLAM
n=8
LORAZEPAM
n=16
Age, years; median (range)
8 (0.6-18)
10 (3-15)
Weight, kg; median (range)
26 (11-83)
29 (13-81)

10. Results Table 1. Dose and patient response MIDAZOLAM LORAZEPAM
# Administrations (# patients)
16 (8)
16 (16)
Dose
0.2 mg/kg
(max 5 mg)
0.1 mg/kg
(max 4 mg)
Time from seizure start to drug administration; median (range)
7 min (5-39)
11 min (5-36)
Time from drug administration to seizure stop; median (range)
0.7 min (0-1.9)
1.7 min (0-5)
# Administrations after which seizures reoccurred within 24 hours
9 (56.3%) 
4 (25%)
# Times second dose administered
3 (19%)
# Times RTT called

11. Discussion
MDZ was administered in a shorter amount of time compared to LZP.
MDZ was effective in terminating SE in the EMU patients.
Because of the shorter duration of action compared to LZP, additional seizures were captured.
For SE, LZP was administered a second time in 3 patients, while MDZ was not administered a second time in any patients.
Rapid Response Team (RRT) was called 3 times for LZP. RRT was not called with any of the MDZ administrations.

12. Conclusions
IV midazolam allows for recording of more seizures after administration allowing for higher yield EMU studies.
EMU order set has now been changed to include IV midazolam as a selection for IV rescue medication.