A protocol for the inhospitalemergency drug managementof convulsive status epilepticusin adults

Shelley Jones,1 Clemens Pahl,2 Eugen Trinka,3 Lina Nashef4

▸ The protocol is free todownload online. Please visit thejournal online (http://dx.doi.org/10.1136/practneurol-2013-000712).

1Pharmacy Department, KingsCollege Hospital NHSFoundation Trust, London, UK2Department of NeuroscienceIntensive Care, Kings CollegeHospital NHS Foundation Trust,London, UK3Department of Neurology,Paracelsus Medical University,Salzburg, Austria4Department of Neurology, KingsCollege Hospital NHSFoundation Trust, London, UK

Correspondence toShelley Jones, Clinical PharmacyTeamleader, Neurosciences,Pharmacy Department, KingsCollege Hospital NHSFoundation Trust, Denmark Hill,London SE5 9RS, UK;shelley.jones1@nhs.net

To cite: Jones S, Pahl C,Trinka E, et al. Pract Neurol2014;14:194–197.

INTRODUCTIONThere are many options for treating con-vulsive status epilepticus but one thing isclear: success is closely associated withtimely intervention and adherence to atreatment protocol.1 Delayed interven-tion leads to treatment resistance andrefractory status. There is little evidencefrom randomised controlled trials, espe-cially for agents used after benzodiaze-pines.2 Therefore, for now, the choicesare mostly based not on Class 1 evidencebut on accumulated and publishedexperience.Management protocols are mandatory

if patients with status epilepticus are toreceive prompt and appropriate treat-ment. Yet many hospitals do not havethese or do not review them regularly.This protocol is adapted from that ofKing’s College Hospital, London, UK,and is in line with the European consen-sus workshop.2 We aim to provide suffi-cient detail to satisfy the treatingphysician’s practical requirements, whilekeeping the protocol simple and easilyaccessible. It should be used with precal-culated dose/weight charts.The treatment pathway comprises first

benzodiazepine (first line), then an intra-venous antiepileptic agent (second line)followed by, where necessary, generalanaesthesia (third line). The choice ofbenzodiazepine and the route usedremains open to discussion. While intra-venous lorazepam remains the first choicein hospital, it is not always available andintravenous access is not always possible.Furthermore, the choice of benzodiazep-ine and its route of administration needrevising as new evidence emerges, par-ticularly given the success of intramuscu-lar midazolam in the prehospital setting.3

To allow for different circumstances,drug availability and access, we listseveral options for stage 1 treatment withbenzodiazepines.With regards to choice of intravenous

antiepileptic drug in the second stage, thelimited available evidence prevents usfrom categorically choosing one overanother. We have, however, suggested anorder of preference; this is influencedmore by local availability and familiaritywith use in the emergency departmentrather than evidence of superiority. Theorder should be reviewed as further evi-dence emerges. Irrespective of the drugchosen, we stress the importance ofgiving adequate loading doses. We haveselected doses in the middle of the usualranges, recognising that these may needto change with time. Where there is aclear response but not full control of sei-zures, in a stable patient, it may be appro-priate to optimise the antiepileptic drugdose, as well as to consider anothersecond stage agent. Otherwise, treatmentshould promptly move to the generalanaesthesia stage. We have not listed laco-samide—available intravenously andoccasionally used in status epilepticus—among the second-stage agents: thisneeds reassessing as more evidenceemerges. It is uncertain whether thedoses need capping, depending onweight. This need probably varies withdifferent drugs and also depends on thedoses per kg body weight used. There islimited information using loading dosesabove 2500 mg for phenytoin, 4000 mgfor levetiracetam and 3000 mg for val-proate: we suggest that their doses shouldbe capped—as is usual clinical practice—though we acknowledge the lack of clearevidence.

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This protocol will hopefully fulfil requirements formost cases of status epilepticus and readers arewelcome to download and adapt it for local use alongwith the precalculated dose-weight charts. It does notaddress cases where seizures continue despite adequateand appropriate general anaesthesia (refractory statusepilepticus),4 which need specialised input, withseveral other possible treatment options considered,including other antiepileptic drugs, ketamine, corti-costeroids, magnesium, intravenous immunoglobulin,ketogenic diet, neurostimulation and, for lesionalcases, surgery.

See the next 2 pages for the Protocol.

Contributors LN conceived the protocol, and LN and SJinitiated the protocol design and content. CP provided expertinformation regarding neuroanaesthetic management of statusepilepticus. ET provided expert review and comments duringprotocol development. LN produced the introductorymanuscript presented with the protocol after discussion withET. All authors contributed to refinement of the protocol andmanuscript and approved the final copy.

Competing interests None.

Provenance and peer review Commissioned; externally peerreviewed. This paper was reviewed by Aiden Neligan, London,UK and Eelco Wijdicks, Rochester, USA.

REFERENCES1 Aranda A, Foucart G, Ducassé JL, et al. Generalized convulsive

status epilepticus management in adults: a cohort study withevaluation of professional practice. Epilepsia2010;51:2159–67.

2 Shorvon S, Baulac M, Cross H, et al. TaskForce on StatusEpilepticus of the ILAE Commission for European Affairs. Thedrug treatment of status epilepticus in Europe: consensusdocument from a workshop at the first London Colloquium onStatus Epilepticus. Epilepsia 2008;49:1277–85.

3 Silbergleit R, Durkalski V, Lowenstein D, et al.; NETTInvestigators. Intramuscular versus intravenous therapy forprehospital status epilepticus. N Engl J Med2012;366:591–600.

4 Shorvon S, Ferlisi M. The treatment of super-refractorystatus epilepticus: a critical review of available therapies and aclinical treatment protocol. Brain 2011;134(Pt 10):2802–18.

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