Comatose Cardiac Arrest Survivors Don’t Need Brain Misfires Suppressed

Comatose survivors of cardiac arrest didn’t benefit from intense treatment of seizure-alike activity on continuous electroencephalographic (EEG) monitoring, the TELSTAR trial showed.

Between people assigned antiseizure medications to suppress aberrant EEG patterns and peers receiving standard care, a poor outcome at 3 months was equally likely per Cerebral Performance Category scale scores (severe disability or worse 90% vs 92%, P=0.68) and mortality rates (80% vs 82%).

The antiseizure treatment group also experienced slightly longer intensive care unit (ICU) stays (8.7 vs 7.5 days) and durations of mechanical ventilation (7.8 vs 6.6 days), according to neurophysiologist Jeannette Hofmeijer, MD, PhD, of the University of Twente in Enschede, the Netherlands, and colleagues, reporting in the New England Journal of Medicine.

Generalized periodic discharges, comprising the bulk of aberrant EEG patterns in TELSTAR, have been hypothesized by some researchers to represent severe ischemic brain damage rather than epilepsy. Subgroup analysis suggested fewer good outcomes with the antiseizure intervention in patients with generalized periodic discharges than in those with other patterns, Hofmeijer’s team found.

“The trial results imply, as have previous studies, that synchronized, low-frequency, rhythmic and periodic EEG patterns signify spontaneously depolarizing cortical neurons that have lost functional organization, are unlikely to be rescued by antiseizure treatment, and are dying,” said neurocritical care physician Eelco Wijdicks, MD, PhD, of Mayo Clinic in Rochester, Minnesota.

“Suppressing these EEG patterns during targeted temperature management after cardiac arrest offers no benefit in a population destined to do poorly,” Wijdicks continued in an accompanying editorial.

However, he suggested it may be advisable to expedite neuroimaging or other tests that have value in predicting poor outcomes after cardiac arrest.

“If corroborating evidence of severe cortical injury appears on these tests or if brain stem reflex responses are persistently absent on clinical examination when sedation is discontinued, there is limited evidence to justify continuing or escalating treatment with antiseizure medications or general anesthetic agents. From there on, discussions about palliative care might be appropriate because other organ systems may also be failing,” Wijdicks wrote.

TELSTAR had been conducted at 11 ICUs in the Netherlands and Belgium from 2014 to 2021. Hofmeijer’s group randomized people to stepwise antiseizure treatment or standard care, with both groups receiving targeted temperature management.

Of over 2,500 cardiac survivors who had continuous EEG recordings, 354 had rhythmic and periodic activity detected on these recordings. The 172 patients included in the study were those who had continuous EEG monitoring started less than 24 hours after the return of spontaneous circulation.

Participants had a median age of 65 years, and 69% were men. Rhythmic or periodic EEG activity was detected a median 35 hours after cardiac arrest. Myoclonus was observed in 62% of people with available data.

Use of antiseizure drugs reached 100% and 10% of treatment and control groups, respectively, as these medications could be used at the clinicians’ discretion as part of standard of care. Complete suppression of rhythmic and periodic EEG activity for at least 48 hours occurred in 56% vs 2% between the two groups.

Most patients received one or two sedatives to support mechanical ventilation or suppress myoclonus. This “may have led to cessation of rhythmic and periodic EEG activity in the standard-care group that reduced the differences in the incidence of EEG and clinical outcomes between the two groups,” Hofmeijer and colleagues cautioned.

A major limitation, they said, was the open-label design of TELSTAR. “Treating physicians in the trial were aware of the trial group assignments, which may have influenced choice regarding medication treatment choices and decisions about withdrawal of care,” the researchers explained.

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