Treatment of electroencephalographic status epilepticus after cardiopulmonary resuscitation (TELSTAR): study protocol for a randomized controlled trial

Barry J Ruijter, Michel J A M van Putten, Janneke Horn, Michiel J Blans, Albertus Beishuizen, Anne-Fleur van Rootselaar, Jeannette Hofmeijer, TELSTAR study group, A Beishuizen, M J Blans, J Hofmeijer, J Horn, M J A M van Putten, A F van Rootselaar, B J Ruijter, W M van den Bergh, J W J Elting, C W E Hoedemaekers, J A M van der Palen, A J C Slooter, I van der Tweel, H B van der Worp, S Boomstra, Barry J Ruijter, Michel J A M van Putten, Janneke Horn, Michiel J Blans, Albertus Beishuizen, Anne-Fleur van Rootselaar, Jeannette Hofmeijer, TELSTAR study group, A Beishuizen, M J Blans, J Hofmeijer, J Horn, M J A M van Putten, A F van Rootselaar, B J Ruijter, W M van den Bergh, J W J Elting, C W E Hoedemaekers, J A M van der Palen, A J C Slooter, I van der Tweel, H B van der Worp, S Boomstra

Abstract

Background: Electroencephalographic (EEG) status epilepticus is described in 10 to 35% of patients with postanoxic encephalopathy after successful cardiopulmonary resuscitation and is associated with case fatality rates of 90 to 100%. It is unclear whether these EEG patterns represent a condition to be treated with anticonvulsants to improve outcome, or an expression of severe ischemic damage, in which treatment is futile.

Methods/design: TELSTAR is a multicenter clinical trial with two parallel groups, randomized treatment allocation, open label treatment, and blinded endpoint evaluation (PROBE design). We aim to enroll 172 adult patients with postanoxic encephalopathy and electroencephalographic status epilepticus after successful cardiopulmonary resuscitation, admitted to the ICU, in whom continuous EEG monitoring is started within 24 hours after admission. Patients are randomly assigned to either medical treatment to suppress all electrographic seizure activity, or no treatment of electroencephalographic status epilepticus. Antiepileptic treatment is based on guidelines for treatment of overt status epilepticus and is started within 3 hours after the diagnosis. If status epilepticus returns during tapering of sedative medication after suppression of all epileptiform activity for 2 × 24 hours, it will be considered refractory. The primary outcome measure is neurological outcome defined as the Cerebral Performance Category (CPC) score at 3 months, dichotomized into 'good' (CPC 1 to 2 = no or moderate neurological disability) and 'poor' (CPC 3 to 5 = severe disability, coma, or death). Secondary outcome measures include mortality and, for patients surviving up to 12 months, cognitive functioning, health related quality of life, and depression.

Trial registration: Clinicaltrials.gov; NCT02056236. Date of registration: 4 February 2014.

Figures

Figure 1
Figure 1
Stepwise treatment approach for electroencephalographic status epilepticus. Each consecutive treatment step is taken when previous steps have failed to suppress electroencephalographic seizure activity. After 24 hours of treatment, sedative agents (thiopental, propofol, and continuously administrated benzodiazepines) will be tapered and intermittently administrated antiepileptic drugs (phenytoin, valproic acid, and levetiracetam) will be continued. If the status epilepticus returns, the treatment procedure will be repeated during another 24 hours. If status epilepticus returns after 2 × 24 hours, it is considered refractory. EEG = Electroencephalography.
Figure 2
Figure 2
Study flow chart. CPC = Cerebral Performance Category; MADRS: Montgomery and Åsberg Depression Rating Scale; SF-36: Medical Outcomes Study 36-item short-form health survey.

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