Guidelines for the management of status epilepticus

420 Viewpoint

Hervé Outina, Hugues Lefortb and Vincent Peignec; the French Group for Status Epilepticus Guidelines

European Journal of Emergency Medicine 2021, 28:420–422

aService de réanimation médico-chirurgicale, Centre hospitalier intercommunal de Poissy, Saint-Germain en Laye, bStructure des urgences, Hôpital d’Instruction des Armées Legouest, Metz and cService de Réanimation, Centre Hospitalier Métropole-Savoie, Chambéry, France

In 2019, The French Intensive Care Society (SRLF) and the French Society of Emergency Medicine (SFMU), along with the Francophone Group of Resuscitation and Paediatric Emergencies (GFRUP), have developed guide- lines to respond to the practical questions raised by status epilepticus management in the prehospital setting, in the emergency department and in the ICU. Twenty-five experts analyzed the literature and formulated recommendations according to the Grade of Recommendation Assessment, Development and Evaluation methodology [1].

This article reports the must-know summary of these guidelines for the initial management of generalized tonic-clonic status epilepticus (GTCSE) by emergency physicians. Additional specific recommendations about children and other types of status epilepticus are availa- ble in the electronic appendix, Supplemental digital con- tent 1, http://links.lww.com/EJEM/A313.

First, experts recommend that GTCSE should be defined as a seizure that lasts at least 5 min with the presence of continuous generalized seizure with motor manifestations, or by the occurrence of several discrete seizures in between which there is no complete recovery of consciousness. The latter is defined by an inability to answer or follow simple orders. Refractory status epilep- ticus should be defined by status epilepticus that persists (clinically or electrically) despite two lines of antiepilep- tic therapy with recommended class and dosage, and ade- quate time for onset of action.

The status epilepticus cause needs to be identified quickly. Several causes may be responsible for a unique status epilepticus event. Experts recommend that the eventuality of psychogenic nonepileptic seizures should systematically be considered throughout the manage- ment of GTCSE.

Treatment of GTCSE must be tapered according to the persistence of the seizures (Fig. 1). Underdosing of antie- pileptic drugs is frequent and should be avoided [2].

Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.euro-emergencymed.com)

Correspondence to Vincent Peigne, MD, Service de Réanimation, Centre Hospitalier Métropole-Savoie, Place Biset, 73000 Chambéry, France

Tel: +33 4 79 96 61 52; e-mail: vincent.peigne@ch-metropole-savoie.fr

Received 14 June 2021 Accepted 17 June 2021

Benzodiazepines have to be used as first-line treatment of GTCSE (grade 1+): intravenous injection of 0.015 mg. kg−1 clonazepam (1 mg for 70 kg; maximum 1.5 mg), or an intramuscular injection of 0.15 mg.kg−1 midazolam (10 mg for 70 kg) (grade 2+). A benzodiazepine injection should be repeated if after 5 min following the first injec- tion if the GTCSE persists (grade 2+).

If the GTCSE persists after 5 min following the sec- ond injection of benzodiazepine, second-line treatment should be administered (grade 1+). Emergency physi- cians can use either sodium valproate (40 mg.kg−1 in 10– 15 min, maximum 3 g; another compound should be used in women of childbearing age), fosphenytoin (20 mg. kg−1 phenytoin equivalent, maximally at 100–150 mg. min−1) or phenytoin (20 mg.kg−1, maximally at 50 mg. min−1 or if >65 years: 15 mg.kg−1 and slow drip), with cardiac monitoring (contraindicated in case of arrhyth- mia or conduction disturbances), phenobarbital (15 mg. kg−1, at 50–100 mg.min−1) or levetiracetam (60 mg.kg−1 over 10 min, maximum 4 g). The full prescribed dose should be administered, even if convulsions stop (grade 2+). Prescription of antiepileptic drugs must respect local regulations (as an example, the maximal dosing of (fos)phenytoin is 15 mg.kg−1 phenytoin equivalent in France).

In the case of persistent convulsive seizures 30 min after administration of the second-line treatment (refractory GTCSE), a coma should be rapidly induced with a third-line general anesthetic (grade 2+). The experts suggest that it is possible to delay coma induc- tion using a further second-line agent if the patient has known epilepsy and lacks any signs or symptoms of a severe brain injury or if there are limitations to the treatment strategy.

One of the most challenging points during GTCSE man- agement is the decision to intubate or not the patient [3]. Intubation may be required by the etiology of status epilepticus (acute severe brain injury) or in the event of refractory GCSE. The experts suggest that intubation of a patient with GTCSE is indicated only in the case of sustained respiratory distress (beyond a few minutes of postcritical stertorous breathing).

DOI: 10.1097/MEJ.0000000000000857

Downloaded from http://journals.lww.com/euro-emergencymed by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 02/10/2022

Fig. 1

Treatment of generalized tonic-clonic status epilepticus. GTCSE, generalized tonic-clonic status epilepticus; IV, intravenous; IM, intramuscular.

Another important question addressed by the experts is the role and timing of electroencephalography (EEG) during GTCSE management. EEG should be performed as soon as possible in the case of (1) no improvement in consciousness after cessation of convulsions, (2) sus- pected psychogenic nonepileptic seizures, metabolic or toxic encephalopathy, subtle or refractory status. A stand- ard EEG should be rapidly recorded after recovery of consciousness following GTCSE.

These new recommendations should allow better man- agement of each status epilepticus patient by emergency physiciansaccordingtograduatedandpersonalizedpro- tocols, modulated according to the type of status epilep- ticus and its etiology. These guidelines update European and American guidelines [4,5] and are in accordance with the most recent works about emergency management of status epilepticus [6,7]. Whether these recommendations

may be applied in different settings in Europe is unknown and warrants further evaluations.

Acknowledgements

This work was sponsored by the French Intensive Care Society (SRLF) and the French Society of Emergency Medicine (SFMU).

The members of the French Group for Status Epilpeticus Guidelines: Papa Gueye, Vincent Alvarez, Stéphane Auvin, Bernard Clair, Philippe Convers, Arielle Crespel, Sophie Demeret, Sophie Dupont, Jean-Christophe Engels, Nicolas Engrand, Yonathan Freund, Philippe Gelisse, Marie Girot, Marie-Odile Marcoux, Vincent Navarro, Andrea Rossetti, Francesco Santoli, Romain Sonneville, William Szurhaj, Pierre Thomas, Luigi Titomanlio, Frédéric Villega.

Management of status epilepticus Outin et al. 421

422 European Journal of Emergency Medicine Conflicts of interest

There are no conflicts of interest.

References

2021, Vol 28 No 6

1 Outin H, Gueye P, Alvarez V, Auvin S, Clair B, Convers P, et al. Recommandations Formalisées d’Experts: Prise en charge des états de mal épileptiques en préhospitalier, en structure d’urgence et en réanimation dans les 48 premières heures. Méd. Intensive Réa 2020; 29:1–37 & Ann Fr Med Urgence 2020; 10:151–186.

2 Sathe AG, Underwood E, Coles LD, Elm JJ, Silbergleit R, Chamberlain JM, et al. Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial. Epilepsia 2021; 62:795–806.

3 Zeidan S, Rohaut B, Outin H, Bolgert F, Houot M, Demoule A, et al. Not all patients with convulsive status epilepticus intubated in pre-hospital

settings meet the criteria for refractory status epilepticus. Seizure 2021;

88:29–35.

4 Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, et al.;

Neurocritical Care Society Status Epilepticus Guideline Writing Committee. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17:3–23.

5 Glauser T, Shinnar S, Gloss D, Alldredge B, Arya R, Bainbridge J, et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr 2016; 16:48–61.

6 Kapur J, Elm J, Chamberlain JM, Barsan W, Cloyd J, Lowenstein D, et al.; NETT and PECARN Investigators. Randomized trial of three anticonvulsant medications for status epilepticus. N Engl J Med 2019; 381:2103–2113.

7 Rossetti AO, Alvarez V. Update on the management of status epilepticus. Curr Opin Neurol 2021; 34:172–181.