Clinical paperAssociation between a quantitative CT scan measure of brain edema and outcome 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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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.