A Comparison of Lorazepam, Diazepam, and Placebo for the Treatment of Out-of-Hospital Status Epilepticus
Brian K. Alldredge, Pharm.D., Alan M. Gelb, M.D., S. Marshal Isaacs, M.D., Megan D. Corry, E.M.T.-P., M.A., Faith Allen, M.D., SueKay Ulrich, R.N., M.S., Mildred D. Gottwald, Pharm.D., Nelda O'Neil, R.N., M.S.N., John M. Neuhaus, Ph.D., Mark R. Segal, Ph.D., and Daniel H. Lowenstein, M.D.
Background It is uncertain whether the administration of benzodiazepinesby paramedics is an effective and safe treatment for out-of-hospitalstatus epilepticus.
Methods We conducted a randomized, double-blind trial to evaluateintravenous benzodiazepines administered by paramedics for thetreatment of out-of-hospital status epilepticus. Adults withprolonged (lasting five minutes or more) or repetitive generalizedconvulsive seizures received intravenous diazepam (5 mg), lorazepam(2 mg), or placebo. An identical second injection was givenif needed.
Results Of the 205 patients enrolled, 66 received lorazepam,68 received diazepam, and 71 received placebo. Status epilepticushad been terminated on arrival at the emergency department inmore patients treated with lorazepam (59.1 percent) or diazepam(42.6 percent) than patients given placebo (21.1 percent) (P=0.001).After adjustment for covariates, the odds ratio for terminationof status epilepticus by the time of arrival in the lorazepamgroup as compared with the placebo group was 4.8 (95 percentconfidence interval, 1.9 to 13.0). The odds ratio was 1.9 (95percent confidence interval, 0.8 to 4.4) in the lorazepam groupas compared with the diazepam group and 2.3 (95 percent confidenceinterval, 1.0 to 5.9) in the diazepam group as compared withthe placebo group. The rates of respiratory or circulatory complicationsafter the study treatment was administered were 10.6 percentfor the lorazepam group, 10.3 percent for the diazepam group,and 22.5 percent for the placebo group (P=0.08).
Conclusions Benzodiazepines are safe and effective when administeredby paramedics for out-of-hospital status epilepticus in adults.Lorazepam is likely to be a better therapy than diazepam.
Source Information
From the Departments of Clinical Pharmacy (B.K.A., M.D.G.), Neurology (B.K.A., F.A., D.H.L.), Surgery (S.M.I.), Epidemiology and Biostatistics (J.M.N., M.R.S.), and Emergency Services (A.M.G., S.M.I., N.O.), San Francisco General Hospital and the University of California, San Francisco; the Emergency Medical Services Division, San Francisco Fire Department, San Francisco (S.M.I., M.D.C.); and the Carondelet Health Network, Tucson, Ariz. (S.U.).
Address reprint requests to Dr. Lowenstein at Gordon Hall, Rm. 103, Harvard Medical School, 25 Shattuck St., Boston, MA 02115, or at daniel_lowenstein{at}hms.harvard.edu.
Yoong, M, Chin, R F M, Scott, R C
(2009). Management of convulsive status epilepticus in children. EDUCATION AND PRACTICE
94: 1-9
[Full Text]
Mallarkey, G.
(2008). What are the therapeutic advances in neurology? Opinions from world experts. Therapeutic Advances in Neurological Disorders
1: 5-12
Rosenow, F., Knake, S.
(2008). Review: Recent and future advances in the treatment of status epilepticus. Therapeutic Advances in Neurological Disorders
1: 25-32
[Abstract]
Yang, H.-w. K., Simoni-Wastila, L., Zuckerman, I. H., Stuart, B.
(2008). Benzodiazepine Use and Expenditures for Medicare Beneficiaries and the Implications of Medicare Part D Exclusions. Psychiatr. Serv.
59: 384-391
[Abstract][Full Text]
Robertson, C. S., McCullough, L. B., Brody, B.
(2007). Finding family for prospective consent in emergency research. Clin Trials
4: 631-637
[Abstract]
Costello, D. J., Cole, A. J.
(2007). Treatment of Acute Seizures and Status Epilepticus. J Intensive Care Med
22: 319-347
[Abstract]
O'Dell, C., O'Hara, K., Kiel, S., McCullough, K.
(2007). Emergency Management of Seizures in the School Setting. The Journal of School Nursing
23: 158-165
[Abstract][Full Text]
McClure, K. B, Delorio, N. M, Schmidt, T. A, Chiodo, G., Gorman, P.
(2007). A qualitative study of institutional review board members' experience reviewing research proposals using emergency exception from informed consent. J. Med. Ethics
33: 289-293
[Abstract][Full Text]
Pellock, J. M.
(2007). Overview: Definitions and Classifications of Seizure Emergencies. J Child Neurol
22: 9S-13S
[Abstract]
Shinnar, S.
(2007). Who Is at Risk for Prolonged Seizures?. J Child Neurol
22: 14S-20S
[Abstract]
O'Hara, K. A.
(2007). First Aid for Seizures: The Importance of Education and Appropriate Response. J Child Neurol
22: 30S-37S
[Abstract]
Glauser, T. A.
(2007). Designing Practical Evidence-Based Treatment Plans for Children With Prolonged Seizures and Status Epilepticus. J Child Neurol
22: 38S-46S
[Abstract]
Cloyd, J.
(2007). Pharmacologic Considerations in the Treatment of Repetitive or Prolonged Seizures. J Child Neurol
22: 47S-52S
[Abstract]
Ramsay, R. E., Shields, W. D., Shinnar, S.
(2007). Special Issues in the Management of Young Children, Older Adults, and the Developmentally Disabled. J Child Neurol
22: 53S-60S
[Abstract]
O'Dell, C., Wheless, J. W., Cloyd, J.
(2007). The Personal and Financial Impact of Repetitive or Prolonged Seizures on the Patient and Family. J Child Neurol
22: 61S-70S
[Abstract]
Chung, S. S., Wang, N. C., Treiman, D. M.
(2007). Comparative Efficacy and Safety of Antiepileptic Drugs for the Treatment of Status Epilepticus. Journal of Pharmacy Practice
20: 137-146
[Abstract]
Welty, T. E
(2006). Neurology and Neurosurgery Clinical Pharmacy Practice: Ignorance, Phobia, or Progress?. The Annals of Pharmacotherapy
40: 2235-2237
[Full Text]
Nandhagopal, R
(2006). Generalised convulsive status epilepticus: an overview. Postgrad. Med. J.
82: 723-732
[Abstract][Full Text]
Rossetti, A. O., Logroscino, G., Bromfield, E. B.
(2005). Refractory Status Epilepticus: Effect of Treatment Aggressiveness on Prognosis. Arch Neurol
62: 1698-1702
[Abstract][Full Text]
Idrees, U., Londner, M.
(2005). Pharmacotherapy Overview of Seizure Management in the Adult Emergency Department. Journal of Pharmacy Practice
18: 394-411
[Abstract]
Walker, M.
(2005). Status epilepticus: an evidence based guide. BMJ
331: 673-677
[Full Text]
Bambauer, K. Z., Sabin, J. E., Soumerai, S. B.
(2005). The Exclusion of Benzodiazepine Coverage in Medicare: Simple Steps for Avoiding a Public Health Crisis. Psychiatr. Serv.
56: 1143-1146
[Full Text]
Marik, P. E., Varon, J.
(2004). The Management of Status Epilepticus. Chest
126: 582-591
[Abstract][Full Text]
Devi, G., Castro, V. J., Huitink, J., Buitelaar, D., Kosten, T., O'Connor, P.
(2003). Management of Drug and Alcohol Withdrawal. NEJM
349: 405-407
[Full Text]
Lathers, C. M., Schraeder, P. L., Claycamp, H. G.
(2003). Clinical Pharmacology of Topiramate versus Lamotrigine versus Phenobarbital: Comparison of Efficacy and Side Effects Using Odds Ratios. J Clin Pharmacol
43: 491-503
[Abstract][Full Text]
Manno, E. M.
(2003). New Management Strategies in the Treatment of Status Epilepticus. Mayo Clin Proc.
78: 508-518
[Abstract]
Stewart, W A, Harrison, R, Dooley, J M
(2002). Respiratory depression in the acute management of seizures. Arch. Dis. Child.
87: 225-226
[Abstract][Full Text]
Parsons, S. J., Tomas, K., Cox, P.
(2002). Review of a Large Clinical Series: Outcome of Pediatric Status Epilepticus Admitted to Intensive Care. J Intensive Care Med
17: 174-179
[Abstract]
Wiebe, S.
(2002). Benzodiazepines were as safe as and more effective than placebo for out-of-hospital status epilepticus. Evid. Based Med.
7: 84-84
[Full Text]
Wu, Y. W., Shek, D. W., Garcia, P. A., Zhao, S., Johnston, S. C.
(2002). Incidence and mortality of generalized convulsive status epilepticus in California. Neurology
58: 1070-1076
[Abstract][Full Text]
Cock, H.R., Schapira, A.H.V.
(2002). A comparison of lorazepam and diazepam as initial therapy in convulsive status epilepticus. QJM
95: 225-231
[Abstract][Full Text]
Bleck, T. P.
(2002). Refractory Status Epilepticus in 2001. Arch Neurol
59: 188-189
[Full Text]
Knopp, R. K., Su, M., Chodosh, A., Nelson, L. S., Alldredge, B. K., Lowenstein, D. H.
(2001). Treatment of Out-of-Hospital Status Epilepticus. NEJM
345: 1913-1914
[Full Text]