Hypoxic-Ischemic Encephalopathy Evaluated by Brain Autopsy and Neuroprognostication After Cardiac Arrest

This cohort study compares the parameters used for prognosis after cardiac arrest with the severity of hypoxic-ischemic encephalopathy shown on autopsy. Importance Neuroprognostication studies are potentially susceptible to a self-fulfilling prophecy as investigated prognostic parameters may affect withdrawal of life-sustaining therapy. Objective To compare the results of prognostic parameters after cardiac arrest (CA) with the histopathologically determined severity of hypoxic-ischemic encephalopathy (HIE) obtained from autopsy results. Design, Setting, and Participants In a retrospective, 3-center cohort study of all patients who died following cardiac arrest during their intensive care unit stay and underwent autopsy between 2003 and 2015, postmortem brain histopathologic findings were compared with post-CA brain computed tomographic imaging, electroencephalographic (EEG) findings, somatosensory-evoked potentials, and serum neuron-specific enolase levels obtained during the intensive care unit stay. Data analysis was conducted from 2015 to 2020. Main Outcomes and Measures The severity of HIE was evaluated according to the selective eosinophilic neuronal death (SEND) classification and patients were dichotomized into categories of histopathologically severe and no/mild HIE. Results Of 187 included patients, 117 were men (63%) and median age was 65 (interquartile range, 58-74) years. Severe HIE was found in 114 patients (61%) and no/mild HIE was identified in 73 patients (39%). Severe HIE was found in all 21 patients with bilaterally absent somatosensory-evoked potentials, all 15 patients with gray-white matter ratio less than 1.10 on brain computed tomographic imaging, all 9 patients with suppressed EEG, 15 of 16 patients with burst-suppression EEG, and all 29 patients with neuron-specific enolase levels greater than 67 mu g/L more than 48 hours after CA without confounders. Three of 7 patients with generalized periodic discharges on suppressed background and 1 patient with burst-suppression EEG had a SEND 1 score (<30% dead neurons) in the cerebral cortex, but higher SEND scores (>30% dead neurons) in other oxygen-sensitive brain regions. Conclusions and Relevance In this study, histopathologic findings suggested severe HIE after cardiac arrest in patients with bilaterally absent cortical somatosensory-evoked potentials, gray-white matter ratio less than 1.10, highly malignant EEG, and serum neuron-specific enolase concentration greater than 67 mu g/L. Question Is there evidence of a self-fulfilling prophecy following current international guidelines of neuroprognostication after cardiac arrest? Findings In this 3-center cohort study of 187 patients who underwent brain autopsy after cardiac arrest, histopathologically determined severe hypoxic-ischemic encephalopathy was noted in patients with bilaterally absent cortical somatosensory-evoked potentials, gray-white matter ratio of brain computed tomographic imaging less than 1.10, highly malignant electroencephalographic patterns, and serum neuron-specific enolase concentration greater than 67 mu g/L. Meaning The findings of this study appear to support the practice of neuroprognostication according to current international guidelines.