6-month Neurological Outcome Research Articles

Abstract 23: The Usefulness of Neuron-Specific Enolase in Cerebrospinal Fluid to Predict Neurological Prognosis in Cardiac Arrest Survivors Who Underwent Target Temperature Management: A Prospective Observational Study

Aim: We aimed to investigate the prognostic performance between serum NSE and cerebrospinal fluid (CSF) NSE for 6-month neurologic outcome in OHCA survivors underwent target temperature management (TTM). Hypothesis: We hypothesized that the NSE levels measured in the CSF would affect the change, earlier and more sensitively than serum, according to severity of hypoxic brain damage. Methods: This single-centre prospective observational study included out-of-hospital cardiac arrest (OHCA) patients underwent TTM. NSE levels were assessed in blood and CSF samples obtained immediately (Day 0), and 24 h (Day 1), 48 h (Day 2), and 72 h (Day 3) after return of spontaneous circulation (ROSC). The primary outcome was the 6-month neurological outcome. Results: We enrolled 34 patients (males, 24; 70.6%), 16 (47.1%) had a poor neurologic outcome. CSF NSE and serum NSE values were significantly higher in the poor outcome group compared to the good outcome group at each time point, except for serum Day 0. CSF NSE and serum NSE had area under curve (AUC) of 0.819-0.972 and 0.648-0.920, respectively. CSF NSE prognostic performances were significant higher than serum NSE at Day 1 and showed excellent AUC values (0.969; 95% Confidential Interval [CI] 0.844-0.999) and high sensitivity (93.8%; 95% CI 69.8-99.8) at 100% specificity. Conclusion: We found CSF NSE values were highly predictive and sensitive markers of 6-month poor neurological outcome in OHCA survivors treated with TTM at Day 1 after ROSC. Thus, CSF NSE level at day 1 after ROSC can be a useful early prognosticator in OHCA survivors.

The usefulness of neuron-specific enolase in cerebrospinal fluid to predict neurological prognosis in cardiac arrest survivors who underwent target temperature management: A prospective observational study

AimCerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels increase ahead of serum NSE levels in patients with severe brain injury. We examined the prognostic performance between CSF NSE and serum NSE levels in out-of-cardiac arrest (OHCA) survivors who had undergone target temperature management (TTM). MethodsThis single-centre prospective observational study included OHCA patients who had undergone TTM. NSE levels were assessed in blood and CSF samples obtained immediately (Day 0), and at 24 h (Day 1), 48 h (Day 2), and 72 h (Day 3) after return of spontaneous circulation (ROSC). The primary outcome was the 6-month neurological outcome. ResultsWe enrolled 34 patients (males, 24; 70.6%), and 16 (47.1%) had a poor neurologic outcome. CSF NSE and serum NSE values were significantly higher in the poor outcome group compared to the good outcome group at each time point, except for serum Day 0. CSF NSE and serum NSE had an area under curve (AUC) of 0.819–0.972 and 0.648–0.920, respectively. CSF NSE prognostic performances were significantly higher than serum NSE levels at Day 1 and showed excellent AUC values (0.969; 95% confidence interval [CI] 0.844–0.999) and high sensitivity (93.8%; 95% CI 69.8–99.8) at 100% specificity. ConclusionWe found CSF NSE values were highly predictive and sensitive markers of 6-month poor neurological outcome in OHCA survivors treated with TTM at Day 1 after ROSC. Therefore, CSF NSE levels at day 1 after ROSC can be a useful early prognosticator in OHCA survivors.

Association between Achievement of Estimated Average Glucose Level and 6-Month Neurologic Outcome in Comatose Cardiac Arrest Survivors: A Propensity Score-Matched Analysis.

We investigated whether achieving estimated average glucose (EAG) levels versus achieving standard glucose levels (180 mg/dL) was associated with neurologic outcome in cardiac arrest survivors. This single-center retrospective observational study included adult comatose cardiac arrest survivors undergoing therapeutic hypothermia (TH) from September 2011 to December 2017. EAG level was calculated using HbA1c obtained after the return of spontaneous circulation (ROSC), and the mean glucose level during TH was calculated. We designated patients to the EAG or standard glucose group according to whether the mean blood glucose level was closer to the EAG level or 180 mg/dL. Patients in the EAG and standard groups were propensity score- matched. The primary outcome was the 6-month neurologic outcome. The secondary outcomes were hypoglycemia (≤70 mg/dL) and serum neuron-specific enolase (NSE) at 48 h after ROSC. Of 384 included patients, 137 (35.7%) had a favorable neurologic outcome. The EAG group had a higher favorable neurologic outcome (104/248 versus 33/136), higher incidence of hypoglycemia (46/248 versus 11/136), and lower NSE level. After propensity score matching, both groups had similar favorable neurologic outcomes (24/93 versus 27/93) and NSE levels; the EAG group had a higher incidence of hypoglycemia (21/93 versus 6/93). Achieving EAG levels was associated with hypoglycemia but not neurologic outcome or serum NSE level.

Usefulness of Intracranial Pressure and Mean Arterial Pressure for Predicting Neurological Prognosis in Cardiac Arrest Survivors Who Undergo Target Temperature Management.

We aimed to compare the relationship of mean arterial pressure (MAP) and intracranial pressure (ICP) to predict the neurological prognosis in cardiac arrest (CA) survivors. We retrospectively examined out-of-hospital CA patients treated with targeted temperature management. ICP was measured using cerebrospinal fluid (CSF) pressure, whereas MAP was measured as blood pressure monitored through the radial or femoral artery during CSF pressure measurement. Primary outcome was 6-month neurological outcome. Of 92 enrolled patients, the favorable outcome group comprised 31 (34%) patients. The median and interquartile range of MAP were significantly higher and ICP was significantly lower in patients with favorable neurological outcomes than in those with unfavorable neurological outcomes (94.3 mmHg [80.0-105.3] vs. 82.0 mmHg [65.3-96.3], p = 0.021 and 9.4 mmHg [10.8-8.7] vs. 18.8 mmHg [20.0-15.7], p < 0.001, respectively). ICP showed the higher area under the receiver operating characteristic curve (area under curve [AUC] = 0.953, 95% confidence interval [CI] = 0.888-0.986) for neurological outcome prediction. MAP showed the lower AUC (0.648, 95% CI = 0.541-0.744). Higher accurate prognosis was predicted by ICP than MAP, and the prognostic performance was good. Prospective multicenter studies are required to confirm these results.

Editors' note: BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis

In the article “BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis,” Sebok et al. reported similar sensitivity of blood oxygen level–dependent cerebrovascular reactivity (BOLD-CVR) in detecting crossed cerebellar diaschisis (CCD) as compared to (15O)-H2O-PET in 25 participants with symptomatic unilateral cerebrovascular steno-occlusive disease and reported that those with CCD had poorer baseline neurologic performance and 3-month neurologic outcome. In response, Reidler et al. question whether CCD was the cause of consequence of poor outcomes, noting that it may be an epiphenomenon of large-volume supratentorial strokes and citing conflicting evidence in the literature about independent association of CCD with post-stroke outcomes. They suggest accounting for lesion volume and distribution in the analyses. In their reply, Niftrik et al. agree that their finding of worse outcome in those with CCD should be cautiously interpreted and investigated in follow-up studies, but argue that supratentorial stroke volume is an inexact measurement, although stroke location would be helpful to examine. They clarify their finding of impaired supratentorial BOLD-CVR in the group with CCD and opine that hemodynamic changes may cause CCD rather than just functional disruption. In the article “BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis,” Sebok et al. reported similar sensitivity of blood oxygen level–dependent cerebrovascular reactivity (BOLD-CVR) in detecting crossed cerebellar diaschisis (CCD) as compared to (15O)-H2O-PET in 25 participants with symptomatic unilateral cerebrovascular steno-occlusive disease and reported that those with CCD had poorer baseline neurologic performance and 3-month neurologic outcome. In response, Reidler et al. question whether CCD was the cause of consequence of poor outcomes, noting that it may be an epiphenomenon of large-volume supratentorial strokes and citing conflicting evidence in the literature about independent association of CCD with post-stroke outcomes. They suggest accounting for lesion volume and distribution in the analyses. In their reply, Niftrik et al. agree that their finding of worse outcome in those with CCD should be cautiously interpreted and investigated in follow-up studies, but argue that supratentorial stroke volume is an inexact measurement, although stroke location would be helpful to examine. They clarify their finding of impaired supratentorial BOLD-CVR in the group with CCD and opine that hemodynamic changes may cause CCD rather than just functional disruption.

Reader response: BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis.

In the article “BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis,” Sebok et al. reported similar sensitivity of blood oxygen level–dependent cerebrovascular reactivity (BOLD-CVR) in detecting crossed cerebellar diaschisis (CCD) as compared to (15O)-H2O-PET in 25 participants with symptomatic unilateral cerebrovascular steno-occlusive disease and reported that those with CCD had poorer baseline neurologic performance and 3-month neurologic outcome. In response, Reidler et al. question whether CCD was the cause of consequence of poor outcomes, noting that it may be an epiphenomenon of large-volume supratentorial strokes and citing conflicting evidence in the literature about independent association of CCD with post-stroke outcomes. They suggest accounting for lesion volume and distribution in the analyses. In their reply, Niftrik et al. agree that their finding of worse outcome in those with CCD should be cautiously interpreted and investigated in follow-up studies, but argue that supratentorial stroke volume is an inexact measurement, although stroke location would be helpful to examine. They clarify their finding of impaired supratentorial BOLD-CVR in the group with CCD and opine that hemodynamic changes may cause CCD rather than just functional disruption.

Author response: BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis.

In the article “BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis,” Sebök et al. reported similar sensitivity of blood oxygen level–dependent cerebrovascular reactivity (BOLD-CVR) in detecting crossed cerebellar diaschisis (CCD) as compared to (15O)-H2O-PET in 25 participants with symptomatic unilateral cerebrovascular steno-occlusive disease and reported that those with CCD had poorer baseline neurologic performance and 3-month neurologic outcome. In response, Reidler et al. question whether CCD was the cause of consequence of poor outcomes, noting that it may be an epiphenomenon of large-volume supratentorial strokes and citing conflicting evidence in the literature about independent association of CCD with post-stroke outcomes. They suggest accounting for lesion volume and distribution in the analyses. In their reply, Niftrik et al. agree that their finding of worse outcome in those with CCD should be cautiously interpreted and investigated in follow-up studies, but argue that supratentorial stroke volume is an inexact measurement, although stroke location would be helpful to examine. They clarify their finding of impaired supratentorial BOLD-CVR in the group with CCD and opine that hemodynamic changes may cause CCD rather than just functional disruption.

Editors' note: Pearls &amp; Oy-sters: Pembrolizumab-induced myasthenia gravis

In the article “Pearls & Oy-sters: Pembrolizumab-induced myasthenia gravis,” Algaeed et al. presented a 73-year-old man who was diagnosed with myasthenia gravis (MG) after receiving pembrolizumab for recurrent melanoma and had positive anti–acetylcholine receptor antibodies (AChRAbs). In response, Robbins et al. note that antibodies like AChRAbs may be less specific for MG after immune checkpoint inhibitor (ICI) therapy and may be a marker for general autoimmunity. They note that AChRAb-positive patients receiving ICI therapy are more likely to develop myositis and that this can clinically resemble MG. In this regard, they note that some reports of ICI-associated MG had normal repetitive nerve stimulation and single-fiber EMG despite severe weakness. Using an illustrative case, they note that the distinction between myositis and MG has important implications for clinical management. In response, Algaeed et al. acknowledge these observations, but note that their patient had unequivocal fatigable ptosis strongly supporting (not pathognomonic in the editor's opinion) the diagnosis of MG. The authors also argue that further understanding of ICI-related autoimmune pathogenesis is needed before concluding that AChRAbs can just be a marker of general autoimmunity. In the article “BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis,” Sebok et al. reported similar sensitivity of blood oxygen level–dependent cerebrovascular reactivity (BOLD-CVR) in detecting crossed cerebellar diaschisis (CCD) as compared to (15O)-H2O-PET in 25 participants with symptomatic unilateral cerebrovascular steno-occlusive disease and reported that those with CCD had poorer baseline neurologic performance and 3-month neurologic outcome. In response, Reidler et al. question whether CCD was the cause of consequence of poor outcomes, noting that it may be an epiphenomenon of large-volume supratentorial strokes and citing conflicting evidence in the literature about independent association of CCD with post-stroke outcomes. They suggest accounting for lesion volume and distribution in the analyses. In their reply, Niftrik et al. agree that their finding of worse outcome in those with CCD should be cautiously interpreted and investigated in follow-up studies, but argue that supratentorial stroke volume is an inexact measurement, although stroke location would be helpful to examine. They clarify their finding of impaired supratentorial BOLD-CVR in the group with CCD and opine that hemodynamic changes may cause CCD rather than just functional disruption.

Author response: Pearls & Oy-sters: Pembrolizumab-induced myasthenia gravis.

In the article “BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis,” Sebok et al. reported similar sensitivity of blood oxygen level–dependent cerebrovascular reactivity (BOLD-CVR) in detecting crossed cerebellar diaschisis (CCD) as compared to (15O)-H2O-PET in 25 participants with symptomatic unilateral cerebrovascular steno-occlusive disease and reported that those with CCD had poorer baseline neurologic performance and 3-month neurologic outcome. In response, Reidler et al. question whether CCD was the cause of consequence of poor outcomes, noting that it may be an epiphenomenon of large-volume supratentorial strokes and citing conflicting evidence in the literature about independent association of CCD with post-stroke outcomes. They suggest accounting for lesion volume and distribution in the analyses. In their reply, Niftrik et al. agree that their finding of worse outcome in those with CCD should be cautiously interpreted and investigated in follow-up studies, but argue that supratentorial stroke volume is an inexact measurement, although stroke location would be helpful to examine. They clarify their finding of impaired supratentorial BOLD-CVR in the group with CCD and opine that hemodynamic changes may cause CCD rather than just functional disruption.

Reader response: Pearls &amp; Oy-sters: Pembrolizumab-induced myasthenia gravis

In the article “BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis,” Sebok et al. reported similar sensitivity of blood oxygen level–dependent cerebrovascular reactivity (BOLD-CVR) in detecting crossed cerebellar diaschisis (CCD) as compared to (15O)-H2O-PET in 25 participants with symptomatic unilateral cerebrovascular steno-occlusive disease and reported that those with CCD had poorer baseline neurologic performance and 3-month neurologic outcome. In response, Reidler et al. question whether CCD was the cause of consequence of poor outcomes, noting that it may be an epiphenomenon of large-volume supratentorial strokes and citing conflicting evidence in the literature about independent association of CCD with post-stroke outcomes. They suggest accounting for lesion volume and distribution in the analyses. In their reply, Niftrik et al. agree that their finding of worse outcome in those with CCD should be cautiously interpreted and investigated in follow-up studies, but argue that supratentorial stroke volume is an inexact measurement, although stroke location would be helpful to examine. They clarify their finding of impaired supratentorial BOLD-CVR in the group with CCD and opine that hemodynamic changes may cause CCD rather than just functional disruption.

Glycated Hemoglobin is Associated with Glycemic Control and 6-Month Neurologic Outcome in Cardiac Arrest Survivors Undergoing Therapeutic Hypothermia.

Glucose control status after cardiac arrest depending on chronic glycemic status and the association between chronic glycemic status and outcome in cardiac arrest survivors are not well known. We investigated the association between glycated hemoglobin (HbA1c) and 6-month neurologic outcome in cardiac arrest survivors undergoing therapeutic hypothermia (TH) and whether mean glucose, area under curve (AUC) of glucose during TH, and neuron-specific enolase (NSE) are different between normal and high HbA1c groups. This retrospective single-center study included adult comatose cardiac arrest survivors who underwent TH from September 2011 to December 2017. HbA1c and glucose were measured after return of spontaneous circulation (ROSC), and normal or high HbA1c was defined using cutoff value of 6.4% of HbA1c. Blood glucose was measured at least every 4h and treated with a written protocol to maintain the range of 80-200mg/dL. Hypoglycemia and hyperglycemia were defined with glucose < 70 or > 180mg/dL. Mean glucose during induction and rewarming phase and AUC of glucose during every 6h of maintenance were calculated, and NSE at 48h after cardiac arrest was recorded. The primary outcome was unfavorable neurologic outcome, defined as Glasgow Pittsburgh Cerebral Performance Category scale 3-5 at 6months after cardiac arrest. Of 384 included patients, 81 (21.1%) had high HbA1c and 247 (64.3%) had an unfavorable neurologic outcome. Patients with high HbA1c were more common in the unfavorable group than in favorable group (27.5% vs 9.5%, p < 0.001), and the unfavorable group had significantly higher HbA1c level (5.8% [5.4-6.8%] vs 5.6% [5.3-6.0%], p = 0.007). HbA1c level was independently associated with worse neurologic outcome (odds ratio 1.414; 95% confidence interval 1.051-1.903). High HbA1c group had higher glucose after ROSC, glucose AUC during maintenance, and rewarming phase than normal HbA1c group. High HbA1c group had significantly higher incidence of hyperglycemia throughout the TH, while normal HbA1c group had significantly higher incidence of normoglycemia. However, no glucose parameter remained as an independent predictor of neurologic outcome after adjustment, irrespective of HbA1c level. NSE showed good prognostic performance (area under curve 0.892; cutoff value 26.3ng/mL). Although NSE level was not different between HbA1c groups, high HbA1c group had higher proportion of patient having NSE over cutoff. Higher HbA1c was independently associated with unfavorable neurologic outcome. Glycemic status during TH was different between normal and high HbA1c groups.

Cost-Effectiveness of Erythropoietin in Traumatic Brain Injury: A Multinational Trial-Based Economic Analysis.

The EPO-TBI multi-national randomized controlled trial found that erythropoietin (EPO), when compared to placebo, did not affect 6-month neurological outcome, but reduced illness severity-adjusted mortality in patients with traumatic brain injury (TBI), making the cost-effectiveness of EPO in TBI uncertain. The current study uses patient-level data from the EPO-TBI trial to evaluate the cost-effectiveness of EPO in patients with moderate or severe TBI from the healthcare payers' perspective. We addressed the issue of transferability in multi-national trials by estimating costs and effects for specific geographical regions of the study (Australia/New Zealand, Europe, and Saudi Arabia). Unadjusted mean quality-adjusted life-years (QALYs; 95% confidence interval [CI]) at 6 months were 0.027 (0.020-0.034; p < 0.001) higher in the EPO group, with an adjusted QALY increment of 0.014 (0.000-0.028; p = 0.04). Mean unadjusted costs (95% CI) were $US5668 (-9191 to -2144; p = 0.002) lower in the treatment group; controlling for baseline IMPACT-TBI score and regional heterogeneity reduced this difference to $2377 (-12,446 to 7693; p = 0.64). For a willingness-to-pay threshold of $US50,000 per QALY, 71.8% of replications were considered cost-effective. Therefore, we did not find evidence that EPO was significantly cost-effective in the treatment of moderate or severe TBI at 6-month follow-up.

Nutrition During Targeted Temperature Management After Cardiac Arrest: Observational Study of Neurological Outcomes and Nutrition Tolerance.

Whether providing nutrition support is beneficial or deleterious during targeted temperature management (TTM) after cardiac arrest is unclear. We therefore performed a retrospective observational study to determine whether early nutrition was beneficial or deleterious during TTM. We retrospectively studied patients admitted to our intensive care unit (ICU) between 2008 and 2014 after successfully resuscitated cardiac arrest. We compared the group given nutrition within 48 hours after ICU admission (E+ group) to the group given nutrition later on or not at all (E- group). Of the 203 included patients, 143 were in the E+ group and 60 in the E- group. The E+ group had a significantly higher proportion of patients with a good 3-month neurological outcome (42.7% vs 16.7%, P < 0.001). The difference remained significant after adjustment on a propensity score (odds ratio, 3.47; 95% confidence interval, 1.48-8.14; P = 0.004). The cumulative energy deficit for an energy goal of 20 kcal/kg/d from admission to day 7 was significantly lower in the E+ group (3304 ± 2863 kcal vs 5017 ± 2655 kcal, P < 0.001). Within the E+ group, the subgroups with nutrition initiation when body temperature was <36°C vs ≥36°C were not significantly different regarding the frequencies of early-onset pneumonia, ventilator-associated pneumonia, vomiting, and prokinetic drug use (all P-values > 0.05). Early nutrition after cardiac arrest during TTM appears safe and may be associated with better neurological outcomes. These findings warrant a randomized controlled trial to resolve the remaining issues.

Usefulness of a quantitative analysis of the cerebrospinal fluid volume proportion in brain computed tomography for predicting neurological prognosis in cardiac arrest survivors who undergo target temperature management

PurposeBrain swelling post-cardiac arrest may affect cerebrospinal fluid volume. We aimed to investigate the prognostic performance of the proportion of cerebrospinal fluid volume (pCSFV) using brain computed tomography (CT) in cardiac arrest survivors. Materials and MethodsThis retrospective multicentre study included adult comatose cardiac arrest survivors who underwent brain CT scan prior to target temperature management (TTM) from 2015 to 2016. Grey-to-white matter ratio (GWR) and pCSFV values were calculated. pCSFV analysis was performed using automated quantitative analysis programming. The primary outcome was a 6-month neurological outcome. ResultsOf 251 patients (median age, 57 years), 173 (68.9%) were male, 87 (34.7%) had a shockable rhythm, and 160 (63.7%) had unfavourable neurological outcomes. GWR but not pCSFV was significantly higher in terms of favourable neurological outcomes (p = .015). pCSFV prognostic performances were similar to GWR, and were poor overall, (0.521; 95% confidence interval [CI], 0.446–0.694 vs. 0.515; 95% CI, 0.441–0.589). After adjusting for covariates, pCSFV but not GWR was independently associated with neurological outcome 6 months following cardiac arrest (p = .049). ConclusionpCSFV was independently associated with neurological outcome 6 months following cardiac arrest, however prognostic performance was not good.

Comparison of extracorporeal and conventional cardiopulmonary resuscitation: a retrospective propensity score matched study

BackgroundThe potential benefit of extracorporeal cardiopulmonary resuscitation (ECPR) compared to conventional CPR (CCPR) for patients with refractory cardiac arrest (CA) remains unclear.MethodsThis study is a retrospective analysis of a prospective database of CA patients, which includes all consecutive adult patients admitted to the Department of Intensive Care after CA between January 2012 and December 2017. The decision to initiate ECPR was made by the attending physician and ECPR performed by the ECPR team, which is composed of ICU physicians. A propensity score was derived using a logistic regression model, including characteristics that varied between groups with a p < 0.10 and were potentially related to outcome. Primary outcomes were survival to ICU discharge and favorable 3-month neurologic outcome, assessed by a Cerebral Performance Category (CPC) score of 1–2.ResultsFrom a total of 635 patients with CA during the study period (ECPR, n = 112), 80 ECPR patients were matched to 80 CCPR patients. The time from arrest to termination of CPR (i.e., return of spontaneous circulation [ROSC], extracorporeal membrane oxygenation [ECMO] initiation, or death) was 54 ± 22 and 54 ± 19 min in the ECPR and CCPR groups, respectively. ROSC rates were 77/80 (96%) for ECPR and 30/80 (38%) for CCPR (p < 0.001). Survival to ICU discharge was 18/80 (23%) vs. 14/80 (18%) in the ECPR and CCPR groups, respectively (p = 0.42). At 3 months, 17/80 (21%) ECPR patients and 9/80 (11%) CCPR patients had a favorable outcome (p = 0.11). Cox regression analysis stratified by matched pairs showed a significantly higher neurologic outcome rate in the ECPR group than in the CCPR group (log-rank test p = 0.003).ConclusionsECPR after CA may be associated with improved long-term neurological outcome.

Association between Early Hyperoxia and Neurologic Outcome in Patient with High Grade Aneurysmal Subarachnoid Hemorrhage

Background: Oxygenation support is a common practice in patients with aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to analyze the association between early hyperoxia and the neurological outcome in patients presenting a High Grade SAH, using the modified Rankin Scale (mRS) at 6 months. Methods: We retrospectively analyzed data of SAH in a single center, retrospective, observational study. The inclusion criteria were patients’ ≥ 18 years-old, under mechanical ventilation upon admission to the intensive care unit (ICU) and presenting an aneurysmal SAH with a WFNS score ≥3. Hyperoxia was defined as PaO2 > 120 mmHg and classified into 3 subgroups: mild (121-200 mmHg), moderate (201-300 mmHg) and severe (> 300 mmHg). Patients with a 6 months-mRS >3 were considered as having a poor outcome. Results: One hundred and thirty-nine patients with aneurysmal SAH were included. 82% of patients were exposed to hyperoxia with predominance of mild hyperoxia (42.8%). A higher yet non-statistical, poor neurologic outcome was identified in the hyperoxic compared to normoxic group (72% vs. 87.7% OR 2.8 [1.02-7.71], p 0.12). Following a multivariate analysis, a statistical trend was identified between the hyperoxic group and a 6-month poor neurological outcome (OR 2.84, 95% CI, 0.99-8.19; p=0.052), but no statistical association was found with delayed cerebral ischemia (OR 1.68, 95% CI, 0.5-5.71, p=0.39) nor with 28-day mortality (OR 2.17, 95% CI, 0.82-5.75, p=0.11). Conclusions: Our findings suggest a statistical trend between early hyperoxia and a poor neurological outcome at 6 months, in patients with a high grade aneurysmal SAH admitted to the ICU. Further, large-scale studies are required to fully evaluate the effects of hyperoxia.

Abstract 290: Fibroblast Growth Factor 21 After Out-of-Hospital Cardiac Arrest

Introduction: Fibroblast growth factor (FGF) 21 is a novel marker of mitochondrial and cellular stress. Due to the pivotal role of mitochondria in oxidative metabolism and oxidative stress we tested the hypothesis that FGF 21 would reflect the severity of hypoxia-reperfusion injury after cardiac arrest. Methods: We measured serum concentration of FGF 21 upon ICU admission and 24, 48 and 72 hours after out-of hospital cardiac arrest (OHCA) in 112 patients. All patients had ventricular fibrillation/tachycardia (VF/VT) as initial rhythm and received targeted temperature management (TTM) of 33 or 36 °C for 24 hours. We defined 6-month Cerebral Performance Category (CPC) 1-2 as good and 3-5 as poor neurologic outcome. We used samples from 40 age- and gender-matched non-critically ill emergency room patients as controls. Group differences were assessed with the Mann Whitney U test and temporal differences with Friedman’s ANOVA and Wilcoxon signed ranks test. Results: The median (inter-quartile range, IQR) FGF 21 concentration at ICU admission was 790 (370-1600) pg/ml and the peak value was 1200 (460-2500) pg/ml at 48 hours. Compared to the ICU admission values, the concentrations in control samples [250 (94-910) pg/ml] were significantly lower (P &lt; 0.001). The ICU admission FGF 21 levels were higher in patients with poor neurologic outcome (P = 0.04) and they correlated weakly with the time from collapse to return of spontaneous circulation (Spearman’s rho 0.23). Serum FGF 21 levels changed over time (P &lt; 0.001). Figure 1 presents serum FGF 21 median levels with IQR (box) and 10-90 percentiles (whiskers). Conclusion: Patients after OHCA have elevated FGF 21 levels after successful resuscitation. Higher ICU admission FGF 21 levels associate with poor 6-month neurologic outcome.

Platelet indices and outcome after cardiac arrest

BackgroundPlatelet variables, including platelet distribution width (PDW) and mean platelet volume (MPV), have been associated with outcome in critically ill patients. We evaluated these variables in patients after cardiac arrest (CA).MethodsAll adult CA patients admitted to the intensive care unit (ICU) over an 8-year period (2006–2014) and treated with targeted temperature management were included. We retrieved all data concerning CA characteristics as well as platelet count, PDW and MPV on the first 2 days of admission. Unfavorable 3-month neurological outcome was defined as a cerebral performance category score of 3–5.ResultsWe included 384 patients (age 62 [52–75] years; 270/384 male): 231 patients (60%) died within 30-days and 246 patients (64%) had an unfavorable 3-month neurological outcome. On admission, platelet count, PDW and MPV were 87 [126–261] *103cells/mm3, 17 [16.3–17.3]% and 8.3 [7.6–9.2] μm3, respectively. Platelet count decreased significantly over the first 2 days, whereas PDW and MPV did not change significantly. There were no significant differences between the values on admission or time-courses of platelet count, PDW or MPV between survivors and non-survivors or between patients with unfavorable and favorable neurological outcome.ConclusionsIn our cohort of post-CA patients, PDW and MPV were not associated with outcome.

Modeling prognostic factors for poor neurological outcome in conservatively treated patients with intracerebral hemorrhage: A focus on TNF-α

ObjectivePrognostic models for Intracerebral hemorrhage (ICH), mainly based on clinical evaluation, have remained inherently confounded by subjective scoring assessments and limited accuracy. In this study, we aimed at assessing the risk for poor outcome after ICH based on peripheral biochemical markers (TNF-α, glutamate and glucose) and radiological variables (both at admission and five days after patient’s care), for modeling purposes of prognostication. Patients and MethodsThe defined initial variables of fifty non-comatose conservatively treated ICH patients without severe complications during the hospitalization process (as intraventricular bleeding, or hematoma expansion) were aligned with the evaluated parameters during re-evaluation (3 months later). A comprehensive statistical approach has been applied by using different modeling strategies for prediction of their functional status and outcome. ResultsHigher blood plasma glutamate, TNF-α and initial ICH volume at admission, as well as higher volumes of ICH and perihematomal edema after five days of care were significantly more likely associated with the poor outcome. Nevertheless, in all of the constructed models, TNF-α was estimated as the only significant predictive risk factor, thus outperforming the capacity of the initial ICH volume and the radiological variables after 5 days, both in terms of prognostication of the functional status and the 3-month neurological outcome. The constructed canonical variable that has fairly marked off the different outcomes was also mainly weighed by the admission TNF-α levels. For the first time, we have carefully developed probability functions for the neurological outcome as a response to the admission TNF-α levels; TNF-α levels >110.35 pg/mL were assessed as an optimal cutoff point fairly identifying patients who will fall into the group with poor outcome. ConclusionsTNF-α based models and admission TNF-α screening might be appropriate as a key component that assists more objective prognostication and management of patient’s care in clinical decision making, as rapid initial diagnosis and concentrated management are crucial for secondary prevention of further devastating neurological impairments after ICH.

Relationship between ventricular characteristics on brain computed tomography and 6-month neurologic outcome in cardiac arrest survivors who underwent targeted temperature management

Aim of the studyBrain swelling after cardiac arrest may affect the ventricles. We aimed to investigate the prognostic performance of ventricular characteristics on brain computed tomography (CT) in cardiac arrest survivors who underwent targeted temperature management (TTM). MethodsThis retrospective cohort study included adult comatose cardiac arrest survivors who underwent brain CT scan within 24 h after resuscitation and underwent TTM from 2014 to 2016. The ventricular areas (lateral, third, and fourth ventricle), distances between the anterior horns of the lateral ventricle (LV) and the posterior horns of the LV, and maximal internal diameter of the skull were measured. Grey-to-white matter ratio (GWR), Evans’ index, and relative LV area were calculated. The primary outcome was a 6-month neurologic outcome. ResultsOf 258 patients, 176 (68.2%) had an unfavourable neurologic outcome. GWR, LV area, third ventricle area, distance between the anterior horns of the LV, distance between the posterior horns of the LV, Evans’ index, and relative LV area were different between neurologic outcome groups. Evans’ index (0.683; 95% confidence interval [CI], 0.623–0.739) and relative LV area (0.670; 95% CI, 0.609–0.727) had higher value of area under the curve than the other ventricular characteristics and showed prognostic performance comparable with GWR (0.600; 95% CI, 0.538–0.661). All ventricular characteristics and GWR were not independently associated with neurologic outcome after adjusting for covariates. ConclusionVentricular characteristics on brain CT were associated with 6 months neurologic outcome in cardiac arrest survivors. Ventricular characteristics were objective measures that had comparable prognostic performance with GWR.