Status epilepticus: continuous midazolam stopped seizures.

Clinical bottom line (level 4)

  1. In patients with refractory generalised status epilepticus, continuous infusion of midazolam stopped seizures, permanently in three out of four patients.
  2. Hypotension occurred in 3/4 cases.
Parent and Lowenstein: Neurology 1994; 44: 1837-1840
Expires December 2003

The study

Case series with ?objective ?blinded outcomes, not adjusted for confounding factors, not validated in an independent set of patients.
Setting: university hospital, USA

4 patients (aged one aged 26 years, one 30 years, one 64 years and one 26 months, 50% male) refractory generalised status epilepticus
Control Group: (n = , analysed):
Experimental Group: (n = 4, 4 analysed): continuous midazolam infusion

100% followed for ?

The evidence

  • patient 1: 26 year old female with renal cell carcinoma and status epilepticus (standard therapy had no effect on seizures). She received a 10 mg iv loading dose of midazolam (200 microg/ kg), followed by midazolam continuous infusion at 0.75 microg/ kg/ min. Seizure activity terminated within 5 minutes. Four hours later, the infusion was increased to 0.9 microg/ kg/ min over 24 hours because of a recurrence. Seizures did not recur after this, and no adverse effects occurred.
  • patient 2: 30 year old female with headache and fever for four days and presented with tonic-clonic seizures. She was unresponsive to standard therapy. Initially given 10 mg iv loading dose, followed by 1.3 microg/ kg/ min midazolam- seizures stopped within 5 minutes. Infusion was adjusted to 1.3 to 2.8 microg/ kg/ min over 8 days. Moderate hypotension occurred. Patient was seizure free for 12 months, when she was treated for persistent complex partial seizures.
  • patient 3: 64 year old man with hyperosmolar hyperglycaemia, and generalised tonic-clonic seizure. Midazolam 17 mg ov bolus, followed by 1.0 microg/ kg/ min continuous infusion, and seizure activity stopped within 90 seconds. Infusion was continued for 34 hours and tapered over 8 hours. No further seizures occurred.
  • patient 4: 26 month old male with head trauma and hyponatraemia. Midazolam 2.5 mg iv bolus, followed by 0.3 to 11 microg/ kg/ min continuous infusion. Seizure activity stopped within 20 minutes. Infusion was discontinued after 12 hours. Hypotension occurred. No further seizures occurred.

    • Comments

    1. The problems of a simple case series are numerous. This data requires confirmation in controlled, preferably randomised studies.

    Citation

    1. Parent JM, and Lowenstein DH: Treatment of refractory generalized status epilepticus with continuous infusion of midazolam. Neurology 1994; 44: 1837-1840
    Contributor: Clare Wotton and Bob Phillips, December 2000
    Reviewer:

    Clinical Question.
    Patient status epilepticus
    Intervention or Exposure midazolam
    Outcome fitting stopped