Status epilepticus: Lorazepam was effective and faster than other medications.

Clinical bottom line (level 1b)

  1. Almost half of patients with generalised status epilepticus stopped fitting on first medication- this fell to only a quarter in patients with coma
  2. Lorazepam was better than phenytoin alone at terminating status epilepticus (NNT = 8 at 60 minutes) but it was not clearly better than diazepam and phenytoin, or phenobarbital
  3. Lorazepam was faster to give than any other medication
Treiman et al: New England Journal of Medicine 1998; 339: 792-798
Expires September 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 16 Veterans Affairs medical centres and 6 university hospitals

518 patients (aged mean age 60 ± 15, 82% male) Generalised convulsive status epilepticus defined as
  • Overt: recurrent convulsions without complete recovery between seizures, or continuous convulsions for > 10 minutes
  • Subtle: continuous coma and ictal changes on EEG


Excluded if
  • had received treatment already and whose seizures had stopped
  • not generalised status epilepticus
  • < 18
  • pregnant
  • neurologic emergency requiring immediate surgical intervention
  • contraindication to therapy with hydantoin, benzodiazepine, or barbiturate
  • previously enrolled


    • Control Group: (n = 145, 145 analysed): phenytoin 18 mg/kg iv. administrated at a maximum of 50 mg/min
    Experimental Group: (n = 146, 146 analysed): diazepam 0.15 mg/kg iv. administrated by a maximum of 5 mg/min followed by phenytoin 18 mg/kg iv. administrated at a maximum of 50 mg/min
    Experimental Group: (n = 146, 146 analysed): lorazepam 0.1 mg/kg iv. administrated at 2 mg/min
    Experimental Group: (n = 133, 133 analysed): phenobarbital 15 mg/kg iv. administrated at a maximum of 100 mg/min

    100% followed for 30 days (Success defined as eliminating clinical and electrical activities within 20 minutes and did not recur for a further 40 minutes)

    The evidence

    Status epilepticus
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    phenytoin vs. diazepam and phenytoin 60 minutes 61
    (42.1%)    		 70
    (48.0%)    		 10.0%
    (-11% to 27%)    		 5.88%
    (-5.54% to 17.3%)    		 17
    (NNT = 6 to infinity;
    NNH = 18 to infinity)
    phenytoin vs. lorazepam 60 minutes 61
    (42.1%)    		 79
    (54.1%)    		 21%
    (1% to 37%)    		 12.04%
    (0.64% to 23.4%)    		 8
    (4 to 156)
    phenytoin vs. phenobarbital 60 minutes 61
    (42.1%)    		 67
    (50.4%)    		 14.0%
    (-7% to 31%)    		 8.31%
    (-3.39% to 20.0%)    		 12
    (NNT = 5 to infinity;
    NNH = 30 to infinity)

    subtle status epilepticus
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    phenytoin vs. diazepam and phenytoin 60 minutes 53
    (51.0%)    		 59
    (60.0%)    		 18%
    (-12% to 40%)    		 8.63%
    (-5.0% to 22.3%)    		 12
    (NNT = 4 to infinity;
    NNH = 20 to infinity)
    phenytoin s. lorazepam 60 minutes 53
    (51.0%)    		 67
    (67.0%)    		 33%
    (5% to 52%)    		 16.0%
    (-.72% to 29.4%)    		 6
    (3 to 37)
    phenytoin vs. phenobarbital 60 minutes 53
    (51.0%)    		 58
    (63.0%)    		 25%
    (-5% to 46%)    		 12.1%
    (-1.69% to 25.9%)    		 8
    (NNT = 4 to infinity;
    NNH = 59 to infinity)

  • Lorazepam was the fastest medication to give (4.7 ± 12 minutes) and treatment with phenytoin the slowest (33 + ± 20 minutes), followed by phenobarbital (17 + ± 12 minutes)
  • No difference in the side-effects were noted between the groups
    • hypoventilation ~10-15 %
    • hypotension ~30-50 %
    • cardiac rhythm disturbance ~ 5-9 %
  • There was no significant difference in the rates of recurrence between the groups at 12 hours (data not given)
  • Patients in overt status were more likely to have been discharged after 30 days than patients with subtle status (50% vs. 8.8%, p < 0.001) and fewer were dead (27% v. 65%)

    • Citation

    1. Treiman DM, Meyers PD, Walton NY, et al: A comparison of four treatments for generalised convulsive status epilepticus. New England Journal of Medicine 1998; 339: 792-798
    Contributor: Chris Ball and Musab Hayatli, October 2000
    Reviewer:

    Clinical Question.
    Patient status epilepticus
    Intervention or Exposure lorazepam
    Comparison diazepam, phenytoin, phenobarbitone
    Outcome cessation of seizure