Status epilepticus: Lorazepam may be as good as diazepam for stopping seizures

Clinical bottom line (level 1b)

  1. Overall, Lorazepam was slightly more effective than diazepam for stopping status epilepticus (NNT = 7 at 20 minutes)
  2. There was no clear difference in adverse effects between the two medications
Leppik et al: Journal of American Medical Association 1983; 249: 1452-1454
Expires September 2003

The study

Double-blinded concealed randomised trial without intention-to-treat
Setting: emergency departments in 3 university hospitals, USA

70 patients (aged mean 53, 72% male) status epilepticus
  • more than three seizures in one hour,
  • two seizures or more in rapid succession without regaining consciousness
  • partial or complex seizures with confusion, or
  • absence seizures with confusion and a characteristic 3 HZ spike


Excluded if
  • terminally ill
  • cardiac arrhythmia
  • hypotensive
  • any metabolic disorder (e.g. hypoglycaemic
  • history of benzodiazepine sensitivity
  • child-bearing potential
  • received diazepam already


    • Control Group: (n = 33, 33 analysed): diazepam 10 mg over 2 minutes
    Experimental Group: (n = 37, 37 analysed): lorazepam 4 mg over 2 minutes
    Patients had a second dose of drug if seizures continued or recurred within 10 minutes. Most had a loading dose of phenytoin
    100% followed for 20 minutes seizures controlled
    Outcome notes:
    • seizure controlled after second injection : 2nd injection was given to only 13 of 14 not responding to first one in placebo group
    • adverse effects : respiratory depression or arrest/hypotension

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    seizures controlled after one injection 10 minutes 19
    (57.9%)    		 29
    (78.4%)    		 49%
    (-6% to 75%)    		 20.8%
    (-0.65% to 42.3%)    		 5
    (NNT = 2 to infinity;
    NNH = 153 to infinity)
    seizure controlled after second injection 20 minutes 6
    (46.2%)    		 4
    (50%)    		 7%
    (-119% to 61%)    		 3.85%
    (-40.1% to 47.8%)    		 26
    (NNT = 2 to infinity;
    NNH = 2 to infinity)
    overall results 20 minutes 25
    (75.8%)    		 33
    (89.1%)    		 55%
    (-35% to 85%)    		 13.4%
    (-4.29% to 31.15%)    		 7
    (NNT = 3 to infinity;
    NNH = 23 to infinity)
    adverse effects 20 minutes 5
    (15.2%)    		 5
    (13.5%)    		 11%
    (-35% to 85%)    		 13.4%
    (-4.29% to 31.2%)    		 61
    (NNT = 6 to infinity;
    NNH = 7 to infinity)

  • not clear if patients were treated similarly by phenytoin loading dose
  • none of diazepam patients suffering adverse effects had any concurrent medical problems, while four in lorazepam had clinically important medical problems.

    • Comments

    1. Study is too small for definitive benefit.

    Citation

    1. Leppik IE, Derivan AT, Homan RW, et al: Double-blind study of Lorazepam and diazepam in status epilepticus. Journal of American Medical Association 1983; 249: 1452-1454
    Contributor: Chris Ball and Musab Hayatli, Unknown Month 2000
    Reviewer:

    Clinical Question.
    Patient status epilepticus
    Intervention or Exposure lorazepam
    Comparison diazepam
    Outcome seizure control, adverse effects