Intranasal vs Buccal vs Intramuscular Midazolam for the Home and Emergency Treatment of Acute Seizures
Condition: Convulsions
MeSH terms: Seizures; Emergencies
Study type: Interventional
Phase: Phase 4

Summary: 
      A randomized controlled clinical trial comparing patient/ ER physician satisfaction and ease
      of administration of 3 non IV routes of midazolam as a rescue medication for seizure control.
      Study population included children with known seizure disorder who were prescribed midazolam
      by pediatric neurologist at home and those presenting to ER with following inclusion and
      exclusion criteria
    

Detailed description: 
      Recruited patients randomized using previously computer-generated randomization tables
      prepared by expert statistician. Study was approved by the faculty ethical committee prior to
      its start and oral informed consent was obtained from the parents. In order to simplify the
      administration process a reference guide was prepared for doses according to weight for each
      of the 3 routes.

      Two major groups were included (home and ER group) and each were subdivided into 3 groups
      according to route of administration

      Children was randomly assigned to receive treatment with intranasal, intramuscular or buccal
      midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation
      of midazolam (5mg/mL) .Intranasal form was administered via a metered dose sprayer at 0.1
      mL/spray (i.e. 0.5mg/spray). If the volume to be administered exceeded 1 mL, then the dose
      was divided between both nostrils to avoid runoff and swallowing. Administration was via
      sprays in each nostril (for nasal) or dripping between the cheek and the gum per side using
      insulin syringe (for buccal) or using 3 mm syringe in the front aspect of thigh for
      intramuscular injection.

      Caretakers who gave the study medication recorded their observations and answered a series of
      questions regarding time to drug administration, seizure cessation time, seizure recurrence,
      need for hospitalization or ER visits and any encountered difficulties or side effects. Ease
      of administration of was rated using a scale prepared by expert statistian from very easy to
      very difficult and overall satisfaction with the medication was rated using 10-point nominal
      scale (0, being not satisfied and 10, greatly satisfied). Seizures that did not cease for ten
      minutes after drug administration and the need to use additional medication was categorized
      as a treatment failure criteria.

      Recruited caretakers who did not spontaneously report the use of the study medication were
      contacted by phone monthly to address any questions and to remind them of the study. Problems
      with different routes of delivery were discussed, for example excessive head movements, ryle
      or upper respiratory tract infections and where possible suggestions and advices to help with
      addressed issue was provided .If a caretaker reported use of study medication at the time of
      the phone call, information was obtained at that time. In this group, not all children
      received a benzodiazepine because of different reasons: unavailability of the drug at home or
      at school, spontaneous resolution of seizures, difficulty in administrating the drug, or
      panic.

      ER doctor given a brief survey after the administration to evaluate sedation, discomfort and
      other adverse effects of the medication as well as any administration difficulties and data
      for other secondary outcomes (need for additional medical support, hospitalization, repeated
      seizures…etc).
    

Intervention name(s): administration of Nasal midazolam in home group as a rescue medication for seizure control.; administration of Buccal midazolam in home group as a rescue medication for seizure control.; administration of intramuscular midazolam in homegroup as a rescue medication for seizure control.; administration of Nasal midazolam in ER group as a rescue medication for seizure control.; administration of Buccal midazolam in ER group as a rescue medication for seizure control.; administration of intramuscular midazolam in ER group as a rescue medication for seizure control.
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Children from home group assigned to receive treatment with intranasal midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) via a metered dose sprayer at 0.1 mL/spray (i.e. 0.5 mg/spray). If the volume to be administered exceeded 1 mL, the dose was divided between both nostrils to avoid runoff and swallowing; Children from home group randomly assigned to receive treatment with buccal midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) via dripping between the cheek and the gum per side using insulin syringe; Children from home group randomly assigned to receive treatment with intramuscular midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) using 3 mm syringe in the front aspect of thigh; Children from the ER group assigned to receive treatment with intranasal midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) via a metered dose sprayer at 0.1 mL/spray (i.e. 0.5 mg/spray). If the volume to be administered exceeded 1 mL, the dose was divided between both nostrils to avoid runoff and swallowing; Children from ER group randomly assigned to receive treatment with buccal midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) via dripping between the cheek and the gum per side using insulin syringe; Children from ER group randomly assigned to receive treatment with intramuscular midazolam with doses of 0.2 mg/kg (maximum, 10 mg) body weight of the standard IV formulation of midazolam (5mg/mL) using 3 mm syringe in the front aspect of thigh
Intervention MeSH terms: Midazolam
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Two major groups were included (home and ER group) and each were subdivided into 3 groups according to route of administration (nasal, buccal and IM)
Masking: None (Open Label)
Primary purpose: Treatment