Early risk stratification for progression to death by neurological criteria following out-of-hospital cardiac arrest

Abstract

Background

Some patients resuscitated from out-of-hospital cardiac arrest (OHCA) progress to death by neurological criteria (DNC). We hypothesized that initial brain imaging, electroencephalography (EEG), and arrest characteristics predict progression to DNC.

Methods

We identified comatose OHCA patients from January 2010 to February 2020 treated at a single quaternary care facility in Western Pennsylvania. We abstracted demographics and arrest characteristics; Pittsburgh Cardiac Arrest Category, initial motor exam and pupillary light reflex; initial brain computed tomography (CT) grey-to-white ratio (GWR), sulcal or basal cistern effacement; initial EEG background and suppression ratio. We used two modeling approaches: fast and frugal tree (FFT) analysis to create an interpretable clinical risk stratification tool and ridge regression for comparison. We used bootstrapping to randomly partition cases into 80% training and 20% test sets and evaluated test set sensitivity and specificity.

Results

We included 1,569 patients, of whom 147 (9%) had diagnosed DNC. Across bootstrap samples, >99% of FFTs included three predictors: sulcal effacement, and in cases without sulcal effacement, the combination of EEG background suppression and GWR ≤ 1.23. This tree had mean sensitivity and specificity of 87% and 81%. Ridge regression with all available predictors had mean sensitivity 91 % and mean specificity 83%. Subjects falsely predicted as likely to progress to DNC generally died of rearrest or withdrawal of life sustaining therapies due to poor neurological prognosis. Two of these cases awakened from coma during the index hospitalization.

Conclusions

Sulcal effacement on presenting brain CT or EEG suppression with GWR ≤ 1.23 predict progression to DNC after OHCA.

Introduction

Even with optimal care, 10–15 % of comatose survivors of out-of-hospital cardiac arrest (OHCA) progress to death by neurological criteria (DNC).1., 2. Early reliable predictors of progression to DNC could inform clinical research, patient care, and shared decision making with surrogates. For example, most neuroprotective therapy trials in OHCA patients are neutral. Coma, defined as an inability to follow commands, is a common but imperfect inclusion criterion that is typically applied without additional stratification of brain injury severity.3., 4. Early identification of patients that ultimately progress to DNC would allow for statistical adjustment or serve as inclusion criteria for trials targeting patients with the most severe injury. From a clinical perspective, expertise in management of severe anoxic injury and determination of DNC is not universal. Early risk stratification may aid in triage, interfacility transfer decision-making as well as early engagement of other support services for families. While early prognostic tests are imperfect, identifying high risk features could may help clinicians convey severity of brain injury to families and surrogates and potential courses. Since post-arrest patients comprise a large proportion of organ donors, reliable prediction of progression to DNC might also allow timely referral to organ procurement organizations to facilitate a smooth transition to post-mortem donor management.1., 5.

Early brain computed tomography (CT) and electroencephalography (EEG) are established prognostic tools after cardiac arrest.⁶ Cytotoxic edema can be quantified on head CT as a ratio of Hounsfield unit density of grey and white matter (GWR), or by qualitative assessment of mass effect on the ambient cisterns or sulci.⁷ Reduction in GWR < 1.10 within 24 hours after arrest reliably predicts poor outcome with extremely low false positive rates.8., 9. EEG is a rich, noninvasive neuromonitoring tool.10., 11. Highly malignant EEG patterns including background suppression are a sign of severe brain injury.12., 13. Prior studies have investigated clinical predictors of progression to DNC after OHCA,14., 15., 16. but have not considered imaging or EEG. We analyzed a cohort of comatose OHCA patients to develop a clinical risk stratification tool to identify cases at high risk of progression to DNC. We hypothesized that features of brain CT and EEG obtained within 24 hours of arrest would identify patients at high risk for progression to DNC. Early identification of post arrest patients at risk for DNC criteria would facilitate control of illness severity in clinical trials, triage to centers capable of caring for patients with the most severe brain injury and expertise in brain death, guide expectations for families, and inform timely referrals to organ procurement organizations.