Coma After Cardiac Arrest: Should Rhythmic and Periodic EEG Activity Be Treated?

Among patients in a comatose state following cardiac arrest with rhythmic and periodic electroencephalographic (EEG) activity, the use of intensive antiseizure therapy over 48 hours or more did not improve neurologic outcomes at 3 months, according to study findings published in The New England Journal of Medicine.

Uncertainty regarding the efficacy of antiseizure treatment has been observed in the results of surveys, which demonstrate that one-third of neurologists use a stepwise antiseizure-medication strategy to suppress epileptiform EEG activity in nonconvulsive status epilepticus and status epilepticus, one-third utilize these agents in a nonstandardized way, and one-third do not use antiseizure medications at all because of the presumed futility of improvement in neurologic outcomes.

The open-label Treatment of Electroencephalographic Status Epilepticus after Cardiopulmonary Resuscitation (TELSTAR) study (ClinicalTrials.gov identifier: NCT02056236) was conducted to evaluate whether the use of intensive, stepwise antiseizure therapy and sedative treatment to suppress rhythmic and periodic EEG patterns detected with the use of continuous EEG monitoring would change the outcomes among these individuals. 

The current study was a pragmatic, multicenter clinical trial with randomized treatment assignments and blinded endpoint assessment at 11 intensive care units (ICUs) in The Netherlands and in Belgium. The researchers compared stepwise treatment to suppress rhythmic and periodic EEG patterns on continuously monitored EEG plus standard care with the use of standard care alone in patients in a comatose state following cardiac arrest.

All eligible participants were 18 years of age or older; were comatose (per the Glasgow Coma Scale, 8 or more; range, 3 to 15, with lower scores indicative of worse response to stimuli) following resuscitation for cardiac arrest; had continuous EEG monitoring initiated less than 24 hours after the return of spontaneous circulation; and had rhythmic or periodic activity on EEG.

A total of 172 patients were enrolled in the study and 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 group; n=88) or to the use of standard care alone (control group individuals; n=84). In both of the groups, standard care included targeted temperature management.

The primary study outcome was neurologic outcome based on the patient’s score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no disability, mild disability, and moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary study outcomes included mortality, length of ICU stay, and duration of use of mechanical ventilation.

The presence of rhythmic or periodic EEG activity was detected at a median of 35 hours following cardiac arrest. Overall, 62% (98 of 157) of participants with available data experienced myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours was reported in 56% (49 of 88) of participants in the antiseizure-treatment arm vs 2% (2 of 83) of individuals in the control arm. At 3 months, 90% (79 of 88) of individuals in the antiseizure-treatment group vs 92% (77 of 84) of individuals in the control group experienced a poor outcome (95% CI, –7 to –11; P =.68).

At 3 months, mortality was 80% in the antiseizure-treatment arm compared with 82% in the control arm. The mean length of ICU stay and mean duration of mechanical ventilation use were slightly lower in the antiseizure-treatment group than in the control group.

A major limitation of the current study is the fact that since mortality within 24 hours was higher among those in the control arm than among those in the antiseizure-treatment arm, the possibility that decisions regarding withdrawal of life-sustaining treatment were not balanced between the trial groups could not be excluded, which was potentially associated with poorer outcomes in the control group.

The researchers concluded that the “…wide confidence interval for the primary outcome may not rule out modest benefit or harm” of intensive antiseizure treatment in this patient population.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

Reference  

Ruijter BJ, Keijzer HM, Tjepkema-Cloostermans MC, et al; TELSTAR Investigators. Treating rhythmic and periodic EEG patterns in comatose survivors of cardiac arrest. N Engl J Med. Published online February 24, 2022. doi:10.1056/NEJMoa2115998