Association between a quantitative CT scan measure of brain edema and outcome after cardiac arrest

doi:10.1016/j.resuscitation.2011.04.001

Resuscitation

Volume 82, Issue 9, September 2011, Pages 1180-1185

https://doi.org/10.1016/j.resuscitation.2011.04.001 Get rights and content

Abstract

Background

Cerebral edema is one physical change associated with brain injury and decreased survival after cardiac arrest. Edema appears on computed tomography (CT) scan of the brain as decreased X-ray attenuation by gray matter. This study tested whether the gray matter attenuation to white matter attenuation ratio (GWR) was associated with survival and functional recovery.

Methods

Subjects were patients hospitalized after cardiac arrest at a single institution between 1/1/2005 and 7/30/2010. Subjects were included if they had non-traumatic cardiac arrest and a non-contrast CT scan within 24 h after cardiac arrest. Attenuation (Hounsfield Units) was measured in gray matter (caudate nucleus, putamen, thalamus, and cortex) and in white matter (internal capsule, corpus callosum and centrum semiovale). The GWR was calculated for basal ganglia and cerebrum. Outcomes included survival and functional status at hospital discharge.

Results

For 680 patients, 258 CT scans were available, but 18 were excluded because of hemorrhage (10), intravenous contrast (3) or technical artifact (5), leaving 240 CT scans for analysis. Lower GWR values were associated with lower initial Glasgow Coma Scale motor score. Overall survival was 36%, but decreased with decreasing GWR. The average of basal ganglia and cerebrum GWR provided the best discrimination. Only 2/58 subjects with average GWR < 1.20 survived and both were treated with hypothermia. The association of GWR with functional outcome was completely explained by mortality when GWR < 1.20.

Conclusions

Subjects with severe cerebral edema, defined by GWR < 1.20, have very low survival with conventional care, including hypothermia. GWR estimates pre-treatment likelihood of survival after cardiac arrest.

Introduction

Cardiac arrest is a significant public health problem, with an annual incidence of over 300,000 cases of out-of-hospital cardiac arrest in North America and a case-fatality rate approaching 95%.¹ Brain injury is a significant contributor to mortality after cardiac arrest. As many as 68% of out-of-hospital cardiac arrest patients and 23% of in-hospital cardiac arrest patients die from brain injury.2, 3 Furthermore, post-arrest brain injury may reduce quality of life in long-term survivors.4, 5, 6, 7 However, the precise mechanisms of post-cardiac arrest brain injury are poorly understood.² A reliable early indicator of neurological injury after cardiac arrest would be desirable because it might allow titration of early interventions, improve stratification of patients in clinical trials, and facilitate ongoing prognostication efforts during intensive care. No clinical sign or test performed shortly after restoration of pulses has been reliably associated with outcome.

Cerebral edema contributes to the pathology of post-cardiac arrest brain injury. This edema appears as a loss of gray matter to white matter differentiation on a cranial computed tomography (CT) scan. For comparison, decreased X-ray attenuation in gray matter is observed during stroke, and this decreased attenuation is correlated with decreased apparent diffusion coefficients on diffusion-weighted MRI.⁸ Two previous studies found that the gray matter to white matter differentiation was significantly lower in post-cardiac arrest patients with poor outcomes (comatose and Glasgow Outcome Scale 1–2, respectively) relative to patients with good outcomes (awake and GOS 3–5, respectively).9, 10 A third study found that attenuation in the putamen and cerebral cortex were decreased in patients with poor outcomes (CPC 4–5) compared to patients with good outcomes (CPC 1–3).¹¹ A separate study found that cerebral edema was associated with poor outcome in pediatric drowning patients.¹² However, the prior studies were of insufficient size to determine the performance characteristics of cranial CT in this population.

Because cranial CT scans are easily obtained in comatose cardiac arrest patients, cerebral edema is a potentially useful early marker for brain injury. A method to stratify patients according to cerebral injury early after cardiac arrest would be useful in clinical trials or in titrating therapy. This study tested the hypothesis that gray matter to white matter differentiation on the initial cranial CT scan was associated with hospital outcome after cardiac arrest. Gray matter to white matter differentiation was quantified by the attenuation in gray matter to the attenuation in white matter ratio (GWR). Outcomes included survival, Cerebral Performance Category (CPC) and Modified Rankin Score (MRS) at hospital discharge.

Section snippets

Patient selection

All patients admitted to UPMC-Presbyterian hospital after in-hospital or out-of-hospital cardiac arrests were entered into a prospective quality improvement database. The Institutional Review Board of the University of Pittsburgh approved retrospective analysis of this database and associated CT scans under a waiver of the requirement to obtain informed consent for a minimal risk study. Inclusion criteria were age >18 years, cardiac arrest and return of spontaneous circulation (ROSC). We defined

Patient demographics

Between January 2005 and July 2010, we treated 680 subjects with in-hospital or out-of-hospital cardiac arrest (Fig. 1). We identified 151 subjects who were awake on presentation and thus did not receive a CT scan (GCS motor score = 6). We excluded subjects with surgical or traumatic causes of arrest (N = 11), withdrawal of care or failure to sustain pulses long enough to receive CT scan (N = 20), and current incarceration (N = 3). If a patient had two cardiac arrests within 6 months, we excluded the

Discussion

This study confirms prior studies that the ratio of gray matter to white matter attenuation on cranial CT images obtained within 24 h after cardiac arrest is associated with survival.9, 10, 11 Extending prior studies, this larger cohort provides more precise description of the performance characteristics of this test. An average GWR less than 1.20 had specificity of 98% for predicting mortality, similar to previous study cutoffs of 1.18 and 1.22, which yielded specificities of 100%.9, 10 Even in

Conclusions

A low GWR (<1.20) measured from early cranial CT scans after cardiac arrest is associated with mortality. The ease of measurement makes GWR a potentially useful tool for predicting lower likelihood of survival in a subset of patients after cardiac arrest when treated conventionally.

Conflict of interest statement

No authors have any conflicts directly related to this work.

Jon C. Rittenberger receives funding from Grant Number 1 KL2 RR024154-02 from the National Center for Research Resources (NCRR), and from an unrestricted grant from the National Association of EMS Physicians/Zoll EMS Resuscitation Research Fellowship.

Clifton W. Callaway receives funding from NHLBI Grant Number 5U01HL077871 for work unrelated to this project.

Acknowledgements

Dr. Rittenberger is supported by Grant Number 1 KL2 RR024154-02 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Dr. Rittenberger is also supported by an unrestricted grant from the National Association of EMS Physicians/Zoll EMS Resuscitation Research Fellowship.

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To determine if the density distribution proportion of Hounsfield unit (HUdp) in head computed tomography (HCT) images can be used to quantitatively measure cerebral edema in survivors of out-of-hospital cardiac arrest (OHCA).
This retrospective observational study included adult comatose OHCA survivors who underwent HCT within 6 h (first) and 72–96 h (second), all performed using the same CT scanner. Semi-automated quantitative analysis was used to identify differences in HUdp at specific HU ranges across the intracranial component based on neurological outcome. Cerebral edema was defined as the increased displacement of the sum of HUdp values (ΔHUdp) at a specific range between two HCT scans. Poor neurological outcome was defined as cerebral performance categories 3–5 at 6 months after OHCA.
Twenty-three (42%) out of 55 patients had poor neurological outcome. Significant HUdp differences were observed between good and poor neurological outcomes in the second HCT scan at HU = 1–14, 23–35, and 39–56 (all P < 0.05). Only the ΔHUdp = 23–35 range showed a significant increase and correlation in the poor neurological outcome group (4.90 vs. -0.72, P < 0.001) with the sum of decreases in the other two ranges (r = 0.97, P < 0.001). Multivariate logistic regression analysis demonstrated a significant association between ΔHUdp = 23–35 range and poor neurological outcomes (adjusted OR, 1.12; 95% CI: 1.02–1.24; P = 0.02).
In this cohort study, the increased displacement in ΔHUdp = 23–35 range is independently associated with poor neurological outcome and provides a quantitative assessment of cerebral edema formation in OHCA survivors.
Simple approach to quantify hypoxic-ischemic brain injury severity from computed tomography imaging files after cardiac arrest
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Grey-white ratio (GWR) can estimate severity of cytotoxic cerebral edema secondary to hypoxic-ischemic brain injury after cardiac arrest and predict progression to death by neurologic criteria (DNC). Current approaches to calculating GWR are not standardized and have variable interrater reliability. We tested if measures of variance of brain density on early computed tomographic (CT) imaging after cardiac arrest could predict DNC.
We performed a retrospective cohort study, identifying post-arrest patients treated between 2011 and 2020 at our single center. We extracted demographic data from our registry and Digital Imaging and Communication in Medicine (DICOM) files for each patient’s first brain CT. We analyzed slices 15–20 of each DICOM, corresponding to the level of the basal ganglia while accommodating differences in patient anatomy. We extracted pixel arrays and converted the radiodensities to Hounsfield units (HU). To focus on brain tissue densities, we excluded HU > 60 and < 10. We calculated the variance of each patient’s HU distribution and the difference between the means of a two-group Gaussian finite mixture model. We compared these novel metrics to existing measures of cerebral edema, then randomly divided our data into 80% training and 20% test sets and used logistic regression to predict DNC.
Of 1,133 included subjects, 457 (40%) were female, mean (standard deviation) age was 58 (16) years, and 115 (10%) progressed to DNC. CTs were obtained a median [interquartile range] of 4.2 [2.8–5.7] hours post-arrest. Our novel measures correlated weakly with GWR. HU variance, but not difference between mixture model means, differed significantly between subjects with and without sulcal or cistern effacement. GWR outperformed our novel measures in predicting progression to DNC with an area under the receiver operating characteristic curve (AUC) of 0.82, compared to HU variance (AUC = 0.73) and the difference between mixture model means (AUC = 0.56).
There are differences in the distribution of HU on post-arrest CT in patients with qualitative measures of cerebral edema. Current methods to quantify cerebral edema outperform simple measures of attenuation variance on early brain CT. Further analyses could investigate if these measures of variance, or other distributional characteristics of brain density, have improved predictive performance on brain CTs obtained later in the clinical course or derived from discrete regions of anatomical interest.
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We included all patients comatose after resuscitation from IHCA or OHCA in this retrospective cohort analysis. We abstracted patient and arrest clinical characteristics, as well as pH and lactate, to estimate systemic illness severity. Brain CT characteristics included quantitative measurement of the grey-to-white ratio (GWR) at the level of the basal ganglia and qualitative assessment of sulcal and cisternal effacement. We compared GWR distribution by stratum (no edema ≥1.30, mild-to-moderate <1.30 and >1.20, severe ≤1.20) and newly identified neurological arrest etiology between IHCA and OHCA groups.
We included 2,306 subjects, of whom 420 (18.2%) suffered IHCA. Fewer IHCA subjects underwent post-arrest brain CT versus OHCA subjects (149 (35.5%) vs 1,555 (82.4%), p < 0.001). Cerebral edema for IHCA versus OHCA was more often absent (60.1% vs. 47.5%) or mild-to-moderate (34.3% vs. 27.9%) and less often severe (5.6% vs. 24.6%). A neurological etiology of arrest was identified on brain CT in 0.5% of IHCA versus 3.2% of OHCA.
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Signs of hypoxic ischaemic encephalopathy (HIE) on head computed tomography (CT) predicts poor neurological outcome after cardiac arrest. We explore whether levels of brain injury markers in blood could predict the likelihood of HIE on CT.
Retrospective analysis of CT performed at 24–168 h post cardiac arrest on clinical indication within the Target Temperature Management after out-of-hospital cardiac arrest-trial. Biomarkers prospectively collected at 24- and 48 h post-arrest were analysed for neuron specific enolase (NSE), neurofilament light (NFL), total-tau and glial fibrillary acidic protein (GFAP). HIE was assessed through visual evaluation and quantitative grey-white-matter ratio (GWR) was retrospectively calculated on Swedish subjects with original images available.
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Coma is common following resuscitation from cardiac arrest. Few data describe the trajectory of recovery the first days following resuscitation. The objective of this study is to describe the evolution in neurological examination during the first 5 days after resuscitation and test if subjects who go on to awaken have different patterns of early recovery.
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The brainstem clinical examination improved during the first 5 days following resuscitation. Brainstem recovery was common in entire cohort and did not differentiate between survivors and non-survivors. Recovery of motor function, however, was associated with survival.
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Cerebral edema following cardiac arrest is a well-known complication of resuscitation and portends a poor outcome. We identified predictors of post-cardiac arrest cerebral edema and tested the association of cerebral edema with discharge outcome.
We performed a retrospective chart review including patients admitted at a single center between January 2015–March 2020 following resuscitation from in-hospital and out-of-hospital cardiac arrest who had head computed tomography imaging. Our primary outcome was moderate-to-severe cerebral edema, which we defined as loss of grey-white differentiation with effacement of the basal and ambient cisterns and radiographic evidence of uncal herniation. We used logistic regression to test associations of demographic information, clinical predictors and comorbidities with moderate-severe cerebral edema.
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^☆: A Spanish translated version of the abstract of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2011.04.001.

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Clinical paperAssociation between a quantitative CT scan measure of brain edema and outcome after cardiac arrest☆

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Patient selection

Patient demographics

Discussion

Conclusions

Conflict of interest statement

Acknowledgements

Am J Cardiol

Resuscitation

Resuscitation

Resuscitation

Resuscitation

Regional variation in out-of-hospital cardiac arrest incidence and outcome

JAMA

Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication

Circulation

Mode of death after admission to an intensive care unit following cardiac arrest

Intensive Care Med

Clinical paper
Association between a quantitative CT scan measure of brain edema and outcome after cardiac arrest☆