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A Randomized Trial for the Treatment of Refractory Status Epilepticus

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Abstract

Background

Refractory status epilepticus (RSE) has a mortality of 16–39%; coma induction is advocated for its management, but no comparative study has been performed. We aimed to assess the effectiveness (RSE control, adverse events) of the first course of propofol versus barbiturates in the treatment of RSE.

Methods

In this randomized, single blind, multi-center trial studying adults with RSE not due to cerebral anoxia, medications were titrated toward EEG burst-suppression for 36–48 h and then progressively weaned. The primary endpoint was the proportion of patients with RSE controlled after a first course of study medication; secondary endpoints included tolerability measures.

Results

The trial was terminated after 3 years, with only 24 patients recruited of the 150 needed; 14 subjects received propofol, 9 barbiturates. The primary endpoint was reached in 43% in the propofol versus 22% in the barbiturates arm (P = 0.40). Mortality (43 vs. 34%; P = 1.00) and return to baseline clinical conditions at 3 months (36 vs. 44%; P = 1.00) were similar. While infections and arterial hypotension did not differ between groups, barbiturate use was associated with a significantly longer mechanical ventilation (P = 0.03). A non-fatal propofol infusion syndrome was detected in one patient, while one subject died of bowel ischemia after barbiturates.

Discussion

Although undersampled, this trial shows significantly longer mechanical ventilation with barbiturates and the occurrence of severe treatment-related complications in both arms. We describe practical issues necessary for the success of future studies needed to improve the current unsatisfactory state of evidence.

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Acknowledgments

The study was supported in part by grants from the Swiss League against Epilepsy, AstraZeneca (Switzerland) and UCB (Switzerland). The six authors do not have any other financial disclosures or conflict of interest. The authors wish to thank Dr Jan Novy (CHUV Lausanne), Katherine Gleason, and Sonia Replansky (BWH Boston, MA) for their help in data acquisition, and Dr Nathan B. Fountain (Charlottesville, VA) for his inputs on the study design. We confirm that we have read the Journal’s position on issues involved in ethical publications and affirm that this report is consistent with those guidelines.

Author information

Authors and Affiliations

  1. Department of Neurology, CHUV et Université de Lausanne, CHUV-BH07, CH-1011, Lausanne, Switzerland

    Andrea O. Rossetti

  2. Department of Neurology, Brigham and Women’s Hospital, Harvard School of Medicine, Boston, MA, USA

    Tracey A. Milligan & Jong Woo Lee

  3. Department of Neurology, HUG, Geneva, Switzerland

    Serge Vulliémoz

  4. Department of Neurology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA

    Costas Michaelides

  5. Department of Neurology, Inselspital, Berne, Switzerland

    Manuel Bertschi

Authors
  1. Andrea O. Rossetti
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  2. Tracey A. Milligan
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  3. Serge Vulliémoz
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  4. Costas Michaelides
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  5. Manuel Bertschi
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  6. Jong Woo Lee
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Corresponding author

Correspondence to Andrea O. Rossetti.

Additional information

This study is dedicated to the memory of Edward B. Bromfield, MD (1951–2009), who greatly contributed to the study design, and was PI of the American side of the study until his death.

Appendix: Clinical Trials. Gov ID: NCT00265616

Appendix: Clinical Trials. Gov ID: NCT00265616

Recruiting Centers (randomized patients). Inselspital Berne, Switzerland, Drs. J. Mathis, A. Nirkko, M. Bertschi (5); Hôpitaux Universitaires de Genève, Geneva, Switzerland, Drs. P. Jallon, S. Vulliémoz, M. Seeck (2); Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, Drs. A.O. Rossetti, J. Novy, C. Cereda, V. Rey, S. Jukopila, M.D. Schaller (10); Brigham and Women’s Hospital, Boston (MA), Drs E.B. Bromfield (deceased), J.W. Lee, T.A. Milligan (5); Massachusetts General Hospital, Boston (MA), Drs. A.J. Cole, C. Michaelides, B. Leeman (2).

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Rossetti, A.O., Milligan, T.A., Vulliémoz, S. et al. A Randomized Trial for the Treatment of Refractory Status Epilepticus. Neurocrit Care 14, 4–10 (2011). https://doi.org/10.1007/s12028-010-9445-z

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  • DOI: https://doi.org/10.1007/s12028-010-9445-z

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