Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest

Barry J Ruijter; Hanneke M Keijzer; Marleen C Tjepkema-Cloostermans; Michiel J Blans; Albertus Beishuizen; Selma C Tromp; Erik Scholten; Janneke Horn; Anne-Fleur van Rootselaar; Marjolein M Admiraal; Walter M van den Bergh; Jan-Willem J Elting; Norbert A Foudraine; Francois H M Kornips; Vivianne H J M van Kranen-Mastenbroek; Rob P W Rouhl; Elsbeth C Thomeer; Walid Moudrous; Frouke A P Nijhuis; Suzanne J Booij; Cornelia W E Hoedemaekers; Jonne Doorduin; Fabio S Taccone; Job van der Palen; Michel J A M van Putten; Jeannette Hofmeijer; TELSTAR Investigators

doi:10.1056/NEJMoa2115998

Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest

Barry J Ruijter, Hanneke M Keijzer, Marleen C Tjepkema-Cloostermans, Michiel J Blans, Albertus Beishuizen, Selma C Tromp, Erik Scholten, Janneke Horn, Anne-Fleur van Rootselaar, Marjolein M Admiraal, Walter M van den Bergh, Jan-Willem J Elting, Norbert A Foudraine, Francois H M Kornips, Vivianne H J M van Kranen-Mastenbroek, Rob P W Rouhl, Elsbeth C Thomeer, Walid Moudrous, Frouke A P Nijhuis, Suzanne J BooijCornelia W E Hoedemaekers, Jonne Doorduin, Fabio S Taccone, Job van der Palen, Michel J A M van Putten, Jeannette Hofmeijer^*, TELSTAR Investigators

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Whether the treatment of rhythmic and periodic electroencephalographic (EEG) patterns in comatose survivors of cardiac arrest improves outcomes is uncertain.

METHODS: We conducted an open-label trial of suppressing rhythmic and periodic EEG patterns detected on continuous EEG monitoring in comatose survivors of cardiac arrest. Patients were randomly assigned in a 1:1 ratio to a stepwise strategy of antiseizure medications to suppress this activity for at least 48 consecutive hours plus standard care (antiseizure-treatment group) or to standard care alone (control group); standard care included targeted temperature management in both groups. The primary outcome was neurologic outcome according to the score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no, mild, or moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary outcomes were mortality, length of stay in the intensive care unit (ICU), and duration of mechanical ventilation.

RESULTS: We enrolled 172 patients, with 88 assigned to the antiseizure-treatment group and 84 to the control group. Rhythmic or periodic EEG activity was detected a median of 35 hours after cardiac arrest; 98 of 157 patients (62%) with available data had myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49 of 88 patients (56%) in the antiseizure-treatment group and in 2 of 83 patients (2%) in the control group. At 3 months, 79 of 88 patients (90%) in the antiseizure-treatment group and 77 of 84 patients (92%) in the control group had a poor outcome (difference, 2 percentage points; 95% confidence interval, -7 to 11; P = 0.68). Mortality at 3 months was 80% in the antiseizure-treatment group and 82% in the control group. The mean length of stay in the ICU and mean duration of mechanical ventilation were slightly longer in the antiseizure-treatment group than in the control group.

CONCLUSIONS: In comatose survivors of cardiac arrest, the incidence of a poor neurologic outcome at 3 months did not differ significantly between a strategy of suppressing rhythmic and periodic EEG activity with the use of antiseizure medication for at least 48 hours plus standard care and standard care alone. (Funded by the Dutch Epilepsy Foundation; TELSTAR ClinicalTrials.gov number, NCT02056236.).

Original language	English
Pages (from-to)	724-734
Number of pages	11
Journal	New England Journal of Medicine
Volume	386
Issue number	8
DOIs	https://doi.org/10.1056/NEJMoa2115998
Publication status	Published - 24 Feb 2022

Keywords

Aged
Anticonvulsants/adverse effects
Coma/etiology
Electroencephalography
Female
Glasgow Coma Scale
Heart Arrest/complications
Humans
Male
Middle Aged
Seizures/diagnosis
Treatment Outcome
MANAGEMENT
EUROPEAN-RESUSCITATION-COUNCIL
GUIDELINES
PROGNOSTIC VALUE
SOCIETY
DISCHARGES
ENCEPHALOPATHY
POSTANOXIC STATUS EPILEPTICUS
THERAPEUTIC HYPOTHERMIA
PREDICTORS

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10.1056/NEJMoa2115998

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Ruijter, B. J., Keijzer, H. M., Tjepkema-Cloostermans, M. C., Blans, M. J., Beishuizen, A., Tromp, S. C., Scholten, E., Horn, J., van Rootselaar, A.-F., Admiraal, M. M., van den Bergh, W. M., Elting, J.-W. J., Foudraine, N. A., Kornips, F. H. M., van Kranen-Mastenbroek, V. H. J. M., Rouhl, R. P. W., Thomeer, E. C., Moudrous, W., Nijhuis, F. A. P., ... TELSTAR Investigators (2022). Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest. New England Journal of Medicine, 386(8), 724-734. https://doi.org/10.1056/NEJMoa2115998

@article{fd0ed4ae1d6f44dda3583bd8ef30e7d8,

title = "Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest",

abstract = "BACKGROUND: Whether the treatment of rhythmic and periodic electroencephalographic (EEG) patterns in comatose survivors of cardiac arrest improves outcomes is uncertain.METHODS: We conducted an open-label trial of suppressing rhythmic and periodic EEG patterns detected on continuous EEG monitoring in comatose survivors of cardiac arrest. Patients were randomly assigned in a 1:1 ratio to a stepwise strategy of antiseizure medications to suppress this activity for at least 48 consecutive hours plus standard care (antiseizure-treatment group) or to standard care alone (control group); standard care included targeted temperature management in both groups. The primary outcome was neurologic outcome according to the score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no, mild, or moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary outcomes were mortality, length of stay in the intensive care unit (ICU), and duration of mechanical ventilation.RESULTS: We enrolled 172 patients, with 88 assigned to the antiseizure-treatment group and 84 to the control group. Rhythmic or periodic EEG activity was detected a median of 35 hours after cardiac arrest; 98 of 157 patients (62%) with available data had myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49 of 88 patients (56%) in the antiseizure-treatment group and in 2 of 83 patients (2%) in the control group. At 3 months, 79 of 88 patients (90%) in the antiseizure-treatment group and 77 of 84 patients (92%) in the control group had a poor outcome (difference, 2 percentage points; 95% confidence interval, -7 to 11; P = 0.68). Mortality at 3 months was 80% in the antiseizure-treatment group and 82% in the control group. The mean length of stay in the ICU and mean duration of mechanical ventilation were slightly longer in the antiseizure-treatment group than in the control group.CONCLUSIONS: In comatose survivors of cardiac arrest, the incidence of a poor neurologic outcome at 3 months did not differ significantly between a strategy of suppressing rhythmic and periodic EEG activity with the use of antiseizure medication for at least 48 hours plus standard care and standard care alone. (Funded by the Dutch Epilepsy Foundation; TELSTAR ClinicalTrials.gov number, NCT02056236.).",

keywords = "Aged, Anticonvulsants/adverse effects, Coma/etiology, Electroencephalography, Female, Glasgow Coma Scale, Heart Arrest/complications, Humans, Male, Middle Aged, Seizures/diagnosis, Treatment Outcome, MANAGEMENT, EUROPEAN-RESUSCITATION-COUNCIL, GUIDELINES, PROGNOSTIC VALUE, SOCIETY, DISCHARGES, ENCEPHALOPATHY, POSTANOXIC STATUS EPILEPTICUS, THERAPEUTIC HYPOTHERMIA, PREDICTORS",

author = "Ruijter, {Barry J} and Keijzer, {Hanneke M} and Tjepkema-Cloostermans, {Marleen C} and Blans, {Michiel J} and Albertus Beishuizen and Tromp, {Selma C} and Erik Scholten and Janneke Horn and {van Rootselaar}, Anne-Fleur and Admiraal, {Marjolein M} and {van den Bergh}, {Walter M} and Elting, {Jan-Willem J} and Foudraine, {Norbert A} and Kornips, {Francois H M} and {van Kranen-Mastenbroek}, {Vivianne H J M} and Rouhl, {Rob P W} and Thomeer, {Elsbeth C} and Walid Moudrous and Nijhuis, {Frouke A P} and Booij, {Suzanne J} and Hoedemaekers, {Cornelia W E} and Jonne Doorduin and Taccone, {Fabio S} and {van der Palen}, Job and {van Putten}, {Michel J A M} and Jeannette Hofmeijer and {TELSTAR Investigators}",

note = "Copyright {\textcopyright} 2022 Massachusetts Medical Society.",

year = "2022",

month = feb,

day = "24",

doi = "10.1056/NEJMoa2115998",

language = "English",

volume = "386",

pages = "724--734",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "MASSACHUSETTS MEDICAL SOCIETY",

number = "8",

}

Ruijter, BJ, Keijzer, HM, Tjepkema-Cloostermans, MC, Blans, MJ, Beishuizen, A, Tromp, SC, Scholten, E, Horn, J, van Rootselaar, A-F, Admiraal, MM, van den Bergh, WM, Elting, J-WJ, Foudraine, NA, Kornips, FHM, van Kranen-Mastenbroek, VHJM , Rouhl, RPW, Thomeer, EC, Moudrous, W, Nijhuis, FAP, Booij, SJ, Hoedemaekers, CWE, Doorduin, J, Taccone, FS, van der Palen, J, van Putten, MJAM, Hofmeijer, J & TELSTAR Investigators 2022, 'Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest', New England Journal of Medicine, vol. 386, no. 8, pp. 724-734. https://doi.org/10.1056/NEJMoa2115998

TY - JOUR

T1 - Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest

AU - Ruijter, Barry J

AU - Keijzer, Hanneke M

AU - Tjepkema-Cloostermans, Marleen C

AU - Blans, Michiel J

AU - Beishuizen, Albertus

AU - Tromp, Selma C

AU - Scholten, Erik

AU - Horn, Janneke

AU - van Rootselaar, Anne-Fleur

AU - Admiraal, Marjolein M

AU - van den Bergh, Walter M

AU - Elting, Jan-Willem J

AU - Foudraine, Norbert A

AU - Kornips, Francois H M

AU - van Kranen-Mastenbroek, Vivianne H J M

AU - Rouhl, Rob P W

AU - Thomeer, Elsbeth C

AU - Moudrous, Walid

AU - Nijhuis, Frouke A P

AU - Booij, Suzanne J

AU - Hoedemaekers, Cornelia W E

AU - Doorduin, Jonne

AU - Taccone, Fabio S

AU - van der Palen, Job

AU - van Putten, Michel J A M

AU - Hofmeijer, Jeannette

AU - TELSTAR Investigators

PY - 2022/2/24

Y1 - 2022/2/24

N2 - BACKGROUND: Whether the treatment of rhythmic and periodic electroencephalographic (EEG) patterns in comatose survivors of cardiac arrest improves outcomes is uncertain.METHODS: We conducted an open-label trial of suppressing rhythmic and periodic EEG patterns detected on continuous EEG monitoring in comatose survivors of cardiac arrest. Patients were randomly assigned in a 1:1 ratio to a stepwise strategy of antiseizure medications to suppress this activity for at least 48 consecutive hours plus standard care (antiseizure-treatment group) or to standard care alone (control group); standard care included targeted temperature management in both groups. The primary outcome was neurologic outcome according to the score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no, mild, or moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary outcomes were mortality, length of stay in the intensive care unit (ICU), and duration of mechanical ventilation.RESULTS: We enrolled 172 patients, with 88 assigned to the antiseizure-treatment group and 84 to the control group. Rhythmic or periodic EEG activity was detected a median of 35 hours after cardiac arrest; 98 of 157 patients (62%) with available data had myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49 of 88 patients (56%) in the antiseizure-treatment group and in 2 of 83 patients (2%) in the control group. At 3 months, 79 of 88 patients (90%) in the antiseizure-treatment group and 77 of 84 patients (92%) in the control group had a poor outcome (difference, 2 percentage points; 95% confidence interval, -7 to 11; P = 0.68). Mortality at 3 months was 80% in the antiseizure-treatment group and 82% in the control group. The mean length of stay in the ICU and mean duration of mechanical ventilation were slightly longer in the antiseizure-treatment group than in the control group.CONCLUSIONS: In comatose survivors of cardiac arrest, the incidence of a poor neurologic outcome at 3 months did not differ significantly between a strategy of suppressing rhythmic and periodic EEG activity with the use of antiseizure medication for at least 48 hours plus standard care and standard care alone. (Funded by the Dutch Epilepsy Foundation; TELSTAR ClinicalTrials.gov number, NCT02056236.).

AB - BACKGROUND: Whether the treatment of rhythmic and periodic electroencephalographic (EEG) patterns in comatose survivors of cardiac arrest improves outcomes is uncertain.METHODS: We conducted an open-label trial of suppressing rhythmic and periodic EEG patterns detected on continuous EEG monitoring in comatose survivors of cardiac arrest. Patients were randomly assigned in a 1:1 ratio to a stepwise strategy of antiseizure medications to suppress this activity for at least 48 consecutive hours plus standard care (antiseizure-treatment group) or to standard care alone (control group); standard care included targeted temperature management in both groups. The primary outcome was neurologic outcome according to the score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no, mild, or moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary outcomes were mortality, length of stay in the intensive care unit (ICU), and duration of mechanical ventilation.RESULTS: We enrolled 172 patients, with 88 assigned to the antiseizure-treatment group and 84 to the control group. Rhythmic or periodic EEG activity was detected a median of 35 hours after cardiac arrest; 98 of 157 patients (62%) with available data had myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49 of 88 patients (56%) in the antiseizure-treatment group and in 2 of 83 patients (2%) in the control group. At 3 months, 79 of 88 patients (90%) in the antiseizure-treatment group and 77 of 84 patients (92%) in the control group had a poor outcome (difference, 2 percentage points; 95% confidence interval, -7 to 11; P = 0.68). Mortality at 3 months was 80% in the antiseizure-treatment group and 82% in the control group. The mean length of stay in the ICU and mean duration of mechanical ventilation were slightly longer in the antiseizure-treatment group than in the control group.CONCLUSIONS: In comatose survivors of cardiac arrest, the incidence of a poor neurologic outcome at 3 months did not differ significantly between a strategy of suppressing rhythmic and periodic EEG activity with the use of antiseizure medication for at least 48 hours plus standard care and standard care alone. (Funded by the Dutch Epilepsy Foundation; TELSTAR ClinicalTrials.gov number, NCT02056236.).

KW - Aged

KW - Anticonvulsants/adverse effects

KW - Coma/etiology

KW - Electroencephalography

KW - Female

KW - Glasgow Coma Scale

KW - Heart Arrest/complications

KW - Humans

KW - Male

KW - Middle Aged

KW - Seizures/diagnosis

KW - Treatment Outcome

KW - MANAGEMENT

KW - EUROPEAN-RESUSCITATION-COUNCIL

KW - GUIDELINES

KW - PROGNOSTIC VALUE

KW - SOCIETY

KW - DISCHARGES

KW - ENCEPHALOPATHY

KW - POSTANOXIC STATUS EPILEPTICUS

KW - THERAPEUTIC HYPOTHERMIA

KW - PREDICTORS

U2 - 10.1056/NEJMoa2115998

DO - 10.1056/NEJMoa2115998

M3 - Article

C2 - 35196426

SN - 0028-4793

VL - 386

SP - 724

EP - 734

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 8

ER -

Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest

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