Skip to main content
Top
Published in: Critical Care 3/2014

Open Access 01-06-2014 | Research

Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study

Authors: Deborah Pugin, Brandon Foreman, Gian Marco De Marchis, Andres Fernandez, J Michael Schmidt, Barry M Czeisler, Stephan A Mayer, Sachin Agarwal, Christine Lesch, Hector Lantigua, Jan Claassen

Published in: Critical Care | Issue 3/2014

Login to get access

Abstract

Introduction

Seizures refractory to third-line therapy are also labeled super-refractory status epilepticus (SRSE). These seizures are extremely difficult to control and associated with poor outcome. We aimed to characterize efficacy and side-effects of continuous infusions of pentobarbital (cIV-PTB) treating SRSE.

Methods

We retrospectively reviewed continuous electroencephalography (cEEG) reports for all adults with RSE treated with cIV-PTB between May 1997 and April 2010 at our institution. Patients with post-anoxic SE and those receiving cIV-PTB for reasons other than RSE were excluded. We collected baseline information, cEEG findings, side-effects and functional outcome at discharge and one year.

Results

Thirty one SRSE patients treated with cIV-PTB for RSE were identified. Mean age was 48 years old (interquartile range (IQR) 28,63), 26% (N = 8) had a history of epilepsy. Median SE duration was 6.5 days (IQR 4,11) and the mean duration of cIV-PTB was 6 days (IQR 3,14). 74% (N = 23) presented with convulsive SE. Underlying etiology was acute symptomatic seizures in 52% (N = 16; 12/16 with encephalitis), remote 30% (N = 10), and unknown 16% (N = 5). cIV-PTB controlled seizures in 90% (N = 28) of patients but seizures recurred in 48% (N = 15) while weaning cIV-PTB, despite the fact that suppression-burst was attained in 90% (N = 28) of patients and persisted >72 hours in 56% (N = 17). Weaning was successful after adding phenobarbital in 80% (12/15 of the patients with withdrawal seizures). Complications during or after cIV-PTB included pneumonia (32%, N = 10), hypotension requiring pressors (29%, N = 9), urinary tract infection (13%, N = 4), and one patient each with propylene glycol toxicity and cardiac arrest. One-third (35%, N = 11) had no identified new complication after starting cIV-PTB. At one year after discharge, 74% (N = 23) were dead or in a state of unresponsive wakefulness, 16% (N = 5) severely disabled, and 10% (N = 3) had no or minimal disability. Death or unresponsive wakefulness was associated with catastrophic etiology (p = 0.03), but none of the other collected variables.

Conclusions

cIV-PTB effectively aborts SRSE and complications are infrequent; outcome in this highly refractory cohort of patients with devastating underlying etiologies remains poor. Phenobarbital may be particularly helpful when weaning cIV-PTB.
Appendix
Available only for authorised users
Literature
1.
go back to reference Holtkamp M, Othman J, Buchheim K, Meierkord H: Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care unit. J Neurol Neurosurg Psychiatry 2005, 76: 534-539.PubMedPubMedCentralCrossRef Holtkamp M, Othman J, Buchheim K, Meierkord H: Predictors and prognosis of refractory status epilepticus treated in a neurological intensive care unit. J Neurol Neurosurg Psychiatry 2005, 76: 534-539.PubMedPubMedCentralCrossRef
2.
go back to reference Lowenstein DH: The management of refractory status epilepticus: an update. Epilepsia 2006, 47: 35-40.PubMedCrossRef Lowenstein DH: The management of refractory status epilepticus: an update. Epilepsia 2006, 47: 35-40.PubMedCrossRef
3.
go back to reference Mayer SA, Claassen J, Lokin J, Mendelsohn F, Dennis LJ, Fitzsimmons BF: Refractory status epilepticus: frequency, risk factors, and impact on outcome. Arch Neurol 2002, 59: 205-210.PubMedCrossRef Mayer SA, Claassen J, Lokin J, Mendelsohn F, Dennis LJ, Fitzsimmons BF: Refractory status epilepticus: frequency, risk factors, and impact on outcome. Arch Neurol 2002, 59: 205-210.PubMedCrossRef
4.
go back to reference Novy J, Logroscino G, Rossetti AO: Refractory status epilepticus: a prospective observational study. Epilepsia 2010, 51: 251-256.PubMedCrossRef Novy J, Logroscino G, Rossetti AO: Refractory status epilepticus: a prospective observational study. Epilepsia 2010, 51: 251-256.PubMedCrossRef
5.
go back to reference Cooper AD, Britton JW, Rabinstein AA: Functional and cognitive outcome in prolonged refractory status epilepticus. Arch Neurol 2009, 66: 1505-1509.PubMedCrossRef Cooper AD, Britton JW, Rabinstein AA: Functional and cognitive outcome in prolonged refractory status epilepticus. Arch Neurol 2009, 66: 1505-1509.PubMedCrossRef
6.
go back to reference Rossetti AO, Logroscino G, Bromfield EB: Refractory status epilepticus: effect of treatment aggressiveness on prognosis. Arch Neurol 2005, 62: 1698-1702.PubMedCrossRef Rossetti AO, Logroscino G, Bromfield EB: Refractory status epilepticus: effect of treatment aggressiveness on prognosis. Arch Neurol 2005, 62: 1698-1702.PubMedCrossRef
7.
go back to reference Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, Laroche SM, Riviello JJ Jr, Shutter L, Sperling MR, Treiman DM, Vespa PM: Neurocritical Care Society Status Epilepticus Guideline Writing Committee: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012, 17: 3-23.PubMedCrossRef Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, Laroche SM, Riviello JJ Jr, Shutter L, Sperling MR, Treiman DM, Vespa PM: Neurocritical Care Society Status Epilepticus Guideline Writing Committee: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012, 17: 3-23.PubMedCrossRef
8.
go back to reference Shorvon S, Ferlisi M: The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain 2011, 134: 2802-2818.PubMedCrossRef Shorvon S, Ferlisi M: The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain 2011, 134: 2802-2818.PubMedCrossRef
9.
go back to reference Claassen J, Hirsch LJ, Mayer SA: Treatment of status epilepticus: a survey of neurologists. J Neurol Sci 2003, 211: 37-41.PubMedCrossRef Claassen J, Hirsch LJ, Mayer SA: Treatment of status epilepticus: a survey of neurologists. J Neurol Sci 2003, 211: 37-41.PubMedCrossRef
10.
go back to reference Meierkord H, Boon P, Engelsen B, Gocke K, Shorvon S, Tinuper P, Holtkamp M: EFNS guideline on the management of status epilepticus in adults. Eur J Neurol 2010, 17: 348-355.PubMedCrossRef Meierkord H, Boon P, Engelsen B, Gocke K, Shorvon S, Tinuper P, Holtkamp M: EFNS guideline on the management of status epilepticus in adults. Eur J Neurol 2010, 17: 348-355.PubMedCrossRef
11.
go back to reference Claassen J, Hirsch LJ, Emerson RG, Mayer SA: Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia 2002, 43: 146-153.PubMedCrossRef Claassen J, Hirsch LJ, Emerson RG, Mayer SA: Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia 2002, 43: 146-153.PubMedCrossRef
12.
go back to reference Shorvon S, Ferlisi M: The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy. Brain 2012, 135: 2314-2328.PubMedCrossRef Shorvon S, Ferlisi M: The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy. Brain 2012, 135: 2314-2328.PubMedCrossRef
13.
go back to reference Claassen J, Hirsch LJ, Emerson RG, Bates JE, Thompson TB, Mayer SA: Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus. Neurology 2001, 57: 1036-1042.PubMedCrossRef Claassen J, Hirsch LJ, Emerson RG, Bates JE, Thompson TB, Mayer SA: Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus. Neurology 2001, 57: 1036-1042.PubMedCrossRef
14.
go back to reference Fernandez A, Lantigua H, Lesch C, Shao B, Foreman B, Schmidt JM, Hirsch LJ, Mayer SA, Claassen J: High-dose midazolam infusion for refractory status epilepticus. Neurology 2014, 82: 359-365.PubMedPubMedCentralCrossRef Fernandez A, Lantigua H, Lesch C, Shao B, Foreman B, Schmidt JM, Hirsch LJ, Mayer SA, Claassen J: High-dose midazolam infusion for refractory status epilepticus. Neurology 2014, 82: 359-365.PubMedPubMedCentralCrossRef
15.
16.
go back to reference Drislane FW, Blum AS, Lopez MR, Gautam S, Schomer DL: Duration of refractory status epilepticus and outcome: loss of prognostic utility after several hours. Epilepsia 2009, 50: 1566-1571.PubMedCrossRef Drislane FW, Blum AS, Lopez MR, Gautam S, Schomer DL: Duration of refractory status epilepticus and outcome: loss of prognostic utility after several hours. Epilepsia 2009, 50: 1566-1571.PubMedCrossRef
17.
go back to reference Kowalski RG, Ziai WC, Rees RN, Werner JK Jr, Kim G, Goodwin H, Geocadin RG: Third-line antiepileptic therapy and outcome in status epilepticus: the impact of vasopressor use and prolonged mechanical ventilation. Crit Care Med 2012, 40: 2677-2684.PubMedCrossRef Kowalski RG, Ziai WC, Rees RN, Werner JK Jr, Kim G, Goodwin H, Geocadin RG: Third-line antiepileptic therapy and outcome in status epilepticus: the impact of vasopressor use and prolonged mechanical ventilation. Crit Care Med 2012, 40: 2677-2684.PubMedCrossRef
18.
go back to reference Krishnamurthy KB, Drislane FW: Relapse and survival after barbiturate anesthetic treatment of refractory status epilepticus. Epilepsia 1996, 37: 863-867.PubMedCrossRef Krishnamurthy KB, Drislane FW: Relapse and survival after barbiturate anesthetic treatment of refractory status epilepticus. Epilepsia 1996, 37: 863-867.PubMedCrossRef
19.
20.
go back to reference Osorio I, Reed RC: Treatment of refractory generalized tonic-clonic status epilepticus with pentobarbital anesthesia after high-dose phenytoin. Epilepsia 1989, 30: 464-471.PubMedCrossRef Osorio I, Reed RC: Treatment of refractory generalized tonic-clonic status epilepticus with pentobarbital anesthesia after high-dose phenytoin. Epilepsia 1989, 30: 464-471.PubMedCrossRef
21.
go back to reference Parviainen I, Uusaro A, Kalviainen R, Kaukanen E, Mervaala E, Ruokonen E: High-dose thiopental in the treatment of refractory status epilepticus in intensive care unit. Neurology 2002, 59: 1249-1251.PubMedCrossRef Parviainen I, Uusaro A, Kalviainen R, Kaukanen E, Mervaala E, Ruokonen E: High-dose thiopental in the treatment of refractory status epilepticus in intensive care unit. Neurology 2002, 59: 1249-1251.PubMedCrossRef
22.
go back to reference Rashkin MC, Youngs C, Penovich P: Pentobarbital treatment of refractory status epilepticus. Neurology 1987, 37: 500-503.PubMedCrossRef Rashkin MC, Youngs C, Penovich P: Pentobarbital treatment of refractory status epilepticus. Neurology 1987, 37: 500-503.PubMedCrossRef
23.
go back to reference Van Ness PC: Pentobarbital and EEG burst suppression in treatment of status epilepticus refractory to benzodiazepines and phenytoin. Epilepsia 1990, 31: 61-67.PubMedCrossRef Van Ness PC: Pentobarbital and EEG burst suppression in treatment of status epilepticus refractory to benzodiazepines and phenytoin. Epilepsia 1990, 31: 61-67.PubMedCrossRef
24.
go back to reference Yaffe K, Lowenstein DH: Prognostic factors of pentobarbital therapy for refractory generalized status epilepticus. Neurology 1993, 43: 895-900.PubMedCrossRef Yaffe K, Lowenstein DH: Prognostic factors of pentobarbital therapy for refractory generalized status epilepticus. Neurology 1993, 43: 895-900.PubMedCrossRef
25.
go back to reference Young GB, Blume WT, Bolton CF, Warren KG: Anesthetic barbiturates in refractory status epilepticus. Can J Neurol Sci 1980, 7: 291-292.PubMed Young GB, Blume WT, Bolton CF, Warren KG: Anesthetic barbiturates in refractory status epilepticus. Can J Neurol Sci 1980, 7: 291-292.PubMed
26.
go back to reference Prasad A, Worrall BB, Bertram EH, Bleck TP: Propofol and midazolam in the treatment of refractory status epilepticus. Epilepsia 2001, 42: 380-386.PubMedCrossRef Prasad A, Worrall BB, Bertram EH, Bleck TP: Propofol and midazolam in the treatment of refractory status epilepticus. Epilepsia 2001, 42: 380-386.PubMedCrossRef
28.
go back to reference Glaser CA, Gilliam S, Honarmand S, Tureen JH, Lowenstein DH, Anderson LJ, Bollen AW, Solbrig MV: Refractory status epilepticus in suspect encephalitis. Neurocrit Care 2008, 9: 74-82.PubMedCrossRef Glaser CA, Gilliam S, Honarmand S, Tureen JH, Lowenstein DH, Anderson LJ, Bollen AW, Solbrig MV: Refractory status epilepticus in suspect encephalitis. Neurocrit Care 2008, 9: 74-82.PubMedCrossRef
29.
go back to reference Koubeissi M, Alshekhlee A: In-hospital mortality of generalized convulsive status epilepticus: a large US sample. Neurology 2007, 69: 886-893.PubMedCrossRef Koubeissi M, Alshekhlee A: In-hospital mortality of generalized convulsive status epilepticus: a large US sample. Neurology 2007, 69: 886-893.PubMedCrossRef
30.
go back to reference Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA: Short-term mortality after a first episode of status epilepticus. Epilepsia 1997, 38: 1344-1349.PubMedCrossRef Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA: Short-term mortality after a first episode of status epilepticus. Epilepsia 1997, 38: 1344-1349.PubMedCrossRef
31.
go back to reference Rossetti AO, Logroscino G, Bromfield EB: A clinical score for prognosis of status epilepticus in adults. Neurology 2006, 66: 1736-1738.PubMedCrossRef Rossetti AO, Logroscino G, Bromfield EB: A clinical score for prognosis of status epilepticus in adults. Neurology 2006, 66: 1736-1738.PubMedCrossRef
32.
go back to reference Towne AR, Pellock JM, Ko D, DeLorenzo RJ: Determinants of mortality in status epilepticus. Epilepsia 1994, 35: 27-34.PubMedCrossRef Towne AR, Pellock JM, Ko D, DeLorenzo RJ: Determinants of mortality in status epilepticus. Epilepsia 1994, 35: 27-34.PubMedCrossRef
Metadata
Title
Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study
Authors
Deborah Pugin
Brandon Foreman
Gian Marco De Marchis
Andres Fernandez
J Michael Schmidt
Barry M Czeisler
Stephan A Mayer
Sachin Agarwal
Christine Lesch
Hector Lantigua
Jan Claassen
Publication date
01-06-2014
Publisher
BioMed Central
Published in
Critical Care / Issue 3/2014
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc13883

Other articles of this Issue 3/2014

Critical Care 3/2014 Go to the issue