ECPR has been increasingly utilized to supply oxygenated blood and hemodynamic support in the absence of spontaneous cardiac circulation. Therefore, ECPR may be considered in settings where it can be rapidly implemented among selected cardiac arrest patients who have not responded to initial conventional CPR [30]. In addition, ECPR had a short-term and long-term survival benefit over conventional CPR in patients with in-hospital cardiac arrest of cardiac origin [14, 31]. Similar to studies on conventional CPR, there have been several studies on neurological prognosis in patients receiving ECPR [12–17]. However, limited data are available on prognostic imaging markers of neurological outcomes after ECPR [18].
In the present study, we evaluated whether GWR, ONSD, and LOB/SE as measurable variables on initial brain CT scans were associated with neurological outcome in patients who underwent ECPR. Although there were no significant differences between the average attenuation in Hounsfield units of each ROI, GWRs (except GWR-CO) on initial brain CT were higher in the good neurological outcome group than in the poor outcome group. ONSD on initial brain CT was correlated closely with neurologic outcome and was greater in the poor neurological outcome group. LOB sign and SE sign were more likely to be detected in the poor neurological outcome group than in the good neurological outcome group. GWR, ONSD, and LOB/SE were associated with neurological outcome after ECPR, and these three CT markers had statistically similar predictive power on poor neurological outcome. Furthermore, a composite of GWR-BG, ONSD, and LOB/SE was a significantly greater predictor of poor neurological outcomes than were each brain CT marker alone.
There have been reports on several predictors of neurological outcome after conventional CPR [2]. Absence of brainstem reflex and motor response other than extensor posturing over a period of 72 h and myoclonic status epilepticus are markers of poor outcomes after cardiac arrest [2, 3]. Elevated serum S-100B and neuron-specific enolase levels and bilaterally absent somatosensory evoked potentials appear to have prognostic value in predicting a poor outcome [2, 3]. In addition, there have been reports of neuroimaging studies such as brain CT, brain magnetic resonance imaging, and magnetic resonance spectroscopy after conventional CPR [2]. In particular, brain CT scans may be helpful for predicting neurological outcomes after ECPR because brain magnetic resonance imaging is an expensive and time-consuming procedure and cannot be immediately performed because of ECMO equipment in patients receiving ECPR [5]. Sedation may confound outcome prediction in survivors of cardiac arrest [32]. Sedative medications are commonly used in comatose CPR survivors for 72 h and are an important confounder [32]. Some clinical signs and examinations such as a motor response to noxious stimuli, corneal reflex, caloric testing, and electroencephalography may also be confounded by sedation [2, 32]. Therefore, brain CT may be more helpful for predicting neurological outcome in ECPR patients under sedation. However, there are limited data on prognostic markers of brain CT for neurological outcomes after ECPR [13, 18].
Some signs on brain CT have been associated with ischemic cerebral insult and poor neurological outcome [5, 7–11]. The LOB and SE signs are associated with ischemic brain damage and poor outcome after cardiac arrest [8]. These signs were also associated with poor neurological outcomes after ECPR in this study. However, identification of these signs may be subject to the abilities of each investigator, and these signs are not quantifiable. GWR was associated with neurological outcome in patients receiving both conventional CPR and ECPR [5, 7–11]. GWR may be explained by the quantitative association of cerebral edema following hypoxic injury with increased intracranial pressure. Similar to other studies, GWRs were significantly different and the attenuation in Hounsfield units in the ROIs were not statistically different between the two groups in this study [5, 9, 10]. In previous studies, average GWR was a better predictor of neurologic outcome than the GWRs of single regions such as BG or the cerebellum alone [5, 9–11]. However, GWR-BG had the largest AUC for prediction of poor neurological outcome among the GWRs in this study. The predictive power of GWR-AV may have been decreased because GWR-CO had little association with poor neurological outcomes in this study. GWRs may be a useful predictor of neurological outcome after ECPR, although the GWR cut-off values were different in different studies [5, 9, 10].
Measurement of ONSD has been proposed as an alternative method for the detection of increased intracranial pressure [11]. The optic nerve is surrounded by cerebrospinal fluid because it is a part of the central nervous system. Therefore, increased intracranial pressure will be transmitted through the subarachnoid space surrounding the optic nerve within the nerve sheath, especially the retrobulbar segment, unless circulation of cerebrospinal fluid is not blocked [11]. ONSD on initial brain CT may be correlated with neurologic outcomes after cardiac arrest [11, 24, 25]. Simultaneous measurement of ONSD on initial CT and intracranial pressure were correlated, and ONSD was indicative of intracranial hypertension in patients with severe traumatic brain injury. ONSD may be a good predictive marker associated with intracranial pressure [25]. Although ONSD is easy to measure on a brain CT scan, it may sometimes be difficult to measure ONSD precisely because of an inappropriate thickness of a CT section or artifacts on brain CT. In addition, similar to GWR, the cut-off values of ONSD differ between studies [11, 24, 25]. We developed a new predictive model for neurological outcomes to overcome a weakness caused by the variation in cut-off values of GWR and ONSD, and a composite of GWR, LOB/SE, and ONSD was a powerful predictor of neurological outcomes compared with each parameter alone. In real-world practice, combined CT parameters could provide improved information on early neurological prognosis in patients undergoing ECPR.
This study had several limitations. First, it was a retrospective review of medical records. Thus, the CPC scale was also retrospectively determined based on medical records. Second, we used a small heterogeneous group of subjects over a large period of time from a single institution. Over this time frame there has also been a significant change in post-arrest management which may affect patients’ outcomes over the study period. Third, the nonrandomized nature of the registry data could have resulted in selection bias. Although brain CT scans were performed within 48 h following ECPR, a major limitation of the study might be that the CT scans are performed in different time settings. However, in this study, AUC of a composite of three markers (GWR-BG?+?ONSD?+?LOB/SE) on brain CT within 15.2 h (median time) was not significantly different from that after 15.2 h (0.886 (95% CI, 0.749–0.963) vs. 0.943 (95% CI, 0.825–0.991); p?=?0.448). One-third of patients received targeted temperature management. Hypothermia can cause coagulopathy, so therapeutic hypothermia was not attempted if patients had substantial bleeding after ECMO insertion. Therefore, surface cooling devices such as Arctic Sun were used on a limited number of patients in our study. Lastly, our study was conducted at a single institution and involved a small number of subjects. Thus, future studies with larger cohorts are needed to confirm these findings.