Skip to main content
SpringerLink
Log in

Phenobarbital Versus Valproate for Generalized Convulsive Status Epilepticus in Adults: A Prospective Randomized Controlled Trial in China

  • Original Research Article
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Objective

Although generalized convulsive status epilepticus (GCSE) is a life-threatening emergency, evidence-based data to guide initial drug treatment choices are lacking in the Chinese population. We conducted this prospective, randomized, controlled trial to evaluate the relative efficacy and safety of intravenous phenobarbital and valproate in patients with GCSE.

Methods

After the failure of first-line diazepam treatment, Chinese adult patients with GCSE were randomized to receive either intravenous phenobarbital (standard doses, low rate) or valproate (standard). Successful treatment was considered when clinical and electroencephalographic seizure activity ceased. Adverse events following treatment, as well as the neurological outcomes at discharge and 3 months later, were also evaluated.

Results

Overall, 73 cases were enrolled in the study. Intravenous phenobarbital was successful in 81.1% of patients, and intravenous valproate was successful in 44.4% of patients (p < 0.05). The relapse rate of status epilepticus within 24 h of receiving phenobarbital (6.7%) was significantly lower than that in patients receiving valproate (31.3%), and the total number of adverse events did not differ significantly between the two groups (p > 0.05). In the phenobarbital group, two patients (5.4%) required ventilation and two patients (5.4%) developed serious hypotension. The neurological outcomes of the phenobarbital group were generally better than those of the valproate group; however, no significant differences were observed between phenobarbital and valproate with respect to mortality (8.1 vs. 16.6%) at discharge, or mortality (16.2 vs. 30.5%) and post-symptomatic epilepsy (26.3 vs. 42.8%) at 3-month follow-up.

Conclusions

Intravenous phenobarbital appears to be more effective than intravenous valproate for Chinese adult patients with GCSE. The occurrence of serious respiratory depression and hypotension caused by phenobarbital was reduced by decreasing the intravenous infusion rate; however, even at a lower infusion rate than typically used in other institutions, intravenous phenobarbital resulted in more serious adverse events than intravenous valproate. The better outcomes in the phenobarbital group compared with the valproate group suggest that phenobarbital should be considered for the early successful treatment of GCSE.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Coeytaux A, Jallon P, Galobardes B, et al. Incidence of status epilepticus in French-speaking Switzerland: (EPISTAR). Neurology. 2000;55:693–7.

    Article  CAS  PubMed  Google Scholar 

  2. Knake S, Rosenow F, Vescovi M, et al. Incidence of status epilepticus in adults in Germany: a prospective, population-based study. Epilepsia. 2001;42:714–8.

    Article  CAS  PubMed  Google Scholar 

  3. Hirsch LJ. Intramuscular versus intravenous benzodiazepines for prehospital treatment of status epilepticus. N Engl J Med. 2012;366:659–60.

    Article  CAS  PubMed  Google Scholar 

  4. Logroscino G, Hesdorffer DC, Cascino G, et al. Time trends in incidence, mortality, and case-fatality after first episode of status epilepticus. Epilepsia. 2001;42:1031–5.

    Article  CAS  PubMed  Google Scholar 

  5. Wu YW, Shek DW, Garcia PA, et al. Incidence and mortality of generalized convulsive status epilepticus in California. Neurology. 2002;58:1070–6.

    Article  CAS  PubMed  Google Scholar 

  6. Li JM, Chen L, Zhou B, et al. Convulsive status epilepticus in adults and adolescents of southwest China: mortality, etiology, and predictors of death. Epilepsy Behav. 2009;14:146–9.

    Article  PubMed  Google Scholar 

  7. Cranford RE, Leppik IE, Patrick B, et al. Intravenous phenytoin in acute treatment of seizures. Neurology. 1979;29:474–9.

    Google Scholar 

  8. Gilad R, Izkovitz N, Dabby R, et al. Treatment of status epilepticus and acute repetitive seizures with i.v. valproic acid vs. phenytoin. Acta Neurol Scand. 2008;118:296–300.

    Article  CAS  PubMed  Google Scholar 

  9. Mehta V, Singhi P, Singhi S. Intravenous sodium valproate versus diazepam infusion for the control of refractory status epilepticus in children: a randomized controlled trial. J Child Neurol. 2007;22:1191–7.

    Article  PubMed  Google Scholar 

  10. Agarwal P, Kumar N, Chandra R, et al. Randomized study of intravenous valproate and phenytoin in status epilepticus. Seizure. 2007;16:527–32.

    Article  PubMed  Google Scholar 

  11. Malamiri RA, Ghaempanah M, Khosroshahi N, et al. Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial. Eur J Paediatr Neurol. 2012;16:536–41.

    Article  PubMed  Google Scholar 

  12. Chen WB, Gao R, Su YY, et al. Valproate versus diazepam for generalized convulsive status epilepticus: a pilot study. Eur J Neurol. 2011;18:1391–6.

    Article  CAS  PubMed  Google Scholar 

  13. Treiman DM, Meyers PD, Walton NY, et al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med. 1998;339:792–8.

    Article  CAS  PubMed  Google Scholar 

  14. Shaner DM, McCurdy SA, Herring MO, et al. Treatment of status epilepticus: a prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin. Neurology. 1988;38:202–7.

    Article  CAS  PubMed  Google Scholar 

  15. Trinka E. What is the relative value of the standard anticonvulsants: phenytoin and fosphenytoin, phenobarbital, valproate, and levetiracetam? Epilepsia. 2009;50:40–3.

    Article  PubMed  Google Scholar 

  16. Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17:3–23.

    Article  PubMed  Google Scholar 

  17. Holtkamp M, Othman J, Buchheim K, et al. Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care unit. J Neurol Neurosurg Psychiatry. 2005;76:534–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Misra UK, Kalita J, Maurya PK. Levetiracetam versus lorazepam in status epilepticus: a randomized, open labeled pilot study. J Neurol. 2012;259:645–8.

    Article  CAS  PubMed  Google Scholar 

  19. Silbergleit R, Lowenstein D, Durkalski V, et al. RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): a double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics. Epilepsia. 2011;52:45–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Swisher CB, Doreswamy M, Gingrich KJ, et al. Phenytoin, levetiracetam, and pregabalin in the acute management of refractory status epilepticus in patients with brain tumors. Neurocrit Care. 2012;16:109–13.

    Article  CAS  PubMed  Google Scholar 

  21. Berning S, Boesebeck F, van Baalen A, et al. Intravenous levetiracetam as treatment for status epilepticus. J Neurol. 2009;256:1634–42.

    Article  CAS  PubMed  Google Scholar 

  22. Eue S, Grumbt M, Muller M, et al. Two years of experience in the treatment of status epilepticus with intravenous levetiracetam. Epilepsy Behav. 2009;15:467–9.

    Article  CAS  PubMed  Google Scholar 

  23. Loddenkemper T, Talos DM, Cleary RT, et al. Subunit composition of glutamate and gamma-aminobutyric acid receptors in status epilepticus. Epilepsy Res. 2014;108:605–15.

    Article  CAS  PubMed  Google Scholar 

  24. Raol YH, Zhang G, Budreck EC, et al. Long-term effects of diazepam and phenobarbital treatment during development on GABA receptors, transporters and glutamic acid decarboxylase. Neuroscience. 2005;132:399–407.

    Article  CAS  PubMed  Google Scholar 

  25. Skerritt JH, Johnston GA. Enhancement of GABA binding by benzodiazepines and related anxiolytics. Eur J Pharmacol. 1983;89:193–8.

    Article  CAS  PubMed  Google Scholar 

  26. Macdonald RL, Kelly KM. Antiepileptic drug mechanisms of action. Epilepsia. 1993;34:S1–8.

    Article  CAS  PubMed  Google Scholar 

  27. Anyanwu E, Harding GF. The involvement of taurine in the action mechanism of sodium valproate (VPA) in the treatment of epilepsy. Acta Physiol Pharmacol Ther Latinoam. 1993;43:20–7.

    CAS  PubMed  Google Scholar 

  28. Aranda A, Foucart G, Ducasse JL, et al. Generalized convulsive status epilepticus management in adults: a cohort study with evaluation of professional practice. Epilepsia. 2010;51:2159–67.

    Article  PubMed  Google Scholar 

  29. Scholtes FB, Renier WO, Meinardi H. Generalized convulsive status epilepticus: causes, therapy, and outcome in 346 patients. Epilepsia. 1994;35:1104–12.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China

    Yingying Su, Gang Liu, Fei Tian, Guoping Ren, Mengdi Jiang, Yunzhou Zhang, Yan Zhang, Hong Ye, Daiquan Gao & Weibi Chen

  2. Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA

    Brian Chun

Authors
  1. Yingying Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fei Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guoping Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mengdi Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Brian Chun
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yunzhou Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hong Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Daiquan Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Weibi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yingying Su.

Ethics declarations

Funding

This study was supported by the National Key Department of Neurology funded by the Chinese Health and Family Planning Committee, and the National Key Department of Critical Care Medicine funded by the Chinese Health and Family Planning Committee.

Conflict of interest

Su Yingying, Liu Gang, TianFei, Ren Guoping, Jiang Mengdi, Brian Chun, Zhang Yunzhou, Zhang Yan, Ye Hong, GaoDaiquan, and Chen Weibi declare they have no conflicts of interest.

Ethical approval

This study was approved by the Ethics Committee of Xuanwu Hospital, Capital Medical University. Written informed consent was obtained from the legal representatives of the patients.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Su, Y., Liu, G., Tian, F. et al. Phenobarbital Versus Valproate for Generalized Convulsive Status Epilepticus in Adults: A Prospective Randomized Controlled Trial in China. CNS Drugs 30, 1201–1207 (2016). https://doi.org/10.1007/s40263-016-0388-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40263-016-0388-6

Keywords

Search

Navigation