Worse Neurological Outcome Research Articles

Delays in thrombolysis during COVID-19 are associated with worse neurological outcomes: the Society of Vascular and Interventional Neurology Multicenter Collaboration

IntroductionWe have demonstrated in a multicenter cohort that the COVID-19 pandemic has led to a delay in intravenous thrombolysis (IVT) among stroke patients. Whether this delay contributes to meaningful short-term outcome differences in these patients warranted further exploration.MethodsWe conducted a nested observational cohort study of adult acute ischemic stroke patients receiving IVT from 9 comprehensive stroke centers across 7 U.S states. Patients admitted prior to the COVID-19 pandemic (1/1/2019–02/29/2020) were compared to patients admitted during the early pandemic (3/1/2020–7/31/2020). Multivariable logistic regression was used to estimate the effect of IVT delay on discharge to hospice or death, with treatment delay on admission during COVID-19 included as an interaction term.ResultsOf the 676 thrombolysed patients, the median age was 70 (IQR 58–81) years, 313 were female (46.3%), and the median NIHSS was 8 (IQR 4–16). Longer treatment delays were observed during COVID-19 (median 46 vs 38 min, p = 0.01) and were associated with higher in-hospital death/hospice discharge irrespective of admission period (OR per hour 1.08, 95% CI 1.01–1.17, p = 0.03). This effect was strengthened after multivariable adjustment (aOR 1.15, 95% CI 1.07–1.24, p < 0.001). There was no interaction of treatment delay on admission during COVID-19 (pinteraction = 0.65). Every one-hour delay in IVT was also associated with 7% lower odds of being discharged to home or acute inpatient rehabilitation facility (aOR 0.93, 95% CI 0.89–0.97, p < 0.001).ConclusionTreatment delays observed during the COVID-19 pandemic led to greater early mortality and hospice care, with a lower probability of discharge to home/rehabilitation facility. There was no effect modification of treatment delay on admission during the pandemic, indicating that treatment delay at any time contributes similarly to these short-term outcomes.

Intensive care\u2013treated cardiac arrest: a retrospective study on the impact of extended age on mortality, neurological outcome, received treatments and healthcare-associated costs

BackgroundCardiac arrest (CA) is a leading cause of death worldwide. As population ages, the need for research focusing on CA in elderly increases. This study investigated treatment intensity, 12-month neurological outcome, mortality and healthcare-associated costs for patients aged over 75 years treated for CA in an intensive care unit (ICU) of a tertiary hospital.MethodsThis single-centre retrospective study included adult CA patients treated in a Finnish tertiary hospital’s ICU between 2005 and 2013. We stratified the study population into two age groups: <75 and ge75 years. We compared interventions defined by the median daily therapeutic scoring system (TISS-76) between the age groups to find differences in treatment intensity. We calculated cost-effectiveness by dividing the total one-year healthcare-associated costs of all patients by the number of survivors with a favourable neurological outcome. Favourable outcome was defined as a cerebral performance category (CPC) of 1–2 at 12 months after cardiac arrest. Logistic regression analysis was used to identify independent associations between age group, mortality and neurological outcome.ResultsThis study included a total of 1,285 patients, of which 212 (16 %) were ge75 years of age. Treatment intensity was lower for the elderly compared to the younger group, with median TISS scores of 116 and 147, respectively (p < 0.001). The effective cost in euros for patients with a good one-year neurological outcome was €168,000 for the elderly and €120,000 for the younger group. At 12 months after CA 24 % of the patients in the elderly group and 47 % of the patients in the younger group had a CPC of 1–2 (p < 0.001). Age was an independent predictor of mortality (multivariate OR = 2.90, 95 % CI: 1.94–4.31, p < 0.001) and neurological outcome (multivariate OR = 3.15, 95 % CI: 2.04–4.86, p < 0.001).ConclusionsThe elderly ICU-treated CA patients in this study had worse neurological outcomes, higher mortality and lower cost-effectiveness than younger patients. Elderly received less intense treatment. Further efforts are needed to recognize the tools for assessing which elderly patients benefit from a more aggressive treatment approach in order to improve the cost-effectiveness of post-CA management.

Association between previous health condition and outcome after cardiac arrest

IntroductionOverall survival of patients with out-of-hospital cardiac arrest (OHCA) remains low, even in those with return of spontaneous circulation (ROSC). In addition to usual prognostic characteristics, patients’ medical history may also influence their outcome. This study aimed to investigate the role of pre-arrest comorbidities on hospital survival, neurological outcome and mode of death in OHCA patients with successful ROSC. MethodsFrom Jan 2012 to Sep 2017, all consecutive non-traumatic OHCA adults, admitted with a stable ROSC were included. Utstein characteristics, circumstances of arrest and interventions were prospectively recorded. Prior comorbidities were measured using the Charlson Comorbidity Index (CCI), and the population was divided into 3 groups (CCI 0, CCI 1–3 and CCI ≥ 4). The association of CCI with early and long-term mortality was assessed using logistic regression and association with withdrawal-of-life sustaining treatments (WLST) or another cause of death using multinomial regression. ResultsDuring the study period, 777 patients were analyzed and 483 (62%) died before hospital discharge, with death rate of 49%, 60% and 70% in CCI 0, CCI 1–3 and CCI ≥ 4 respectively. After adjustment, an increase CCI was significantly associated with in-hospital mortality (OR = 2.47 [1.35–4.52], p = 0.001 for CCI 1–3; OR = 2.82 [1.49–5.33], p = 0.003 for CCI ≥ 4; ref = CCI 0). Other independent predictors were non-shockable rhythm (OR = 3.23 [2.08–5]), lack of bystander CPR (OR = 1.96 [1.22–3.13]), epinephrine dose ≥ 2 mg (OR = 5.56 [3.70–8.33]), CA to CPR ≥ 5 min (OR = 1.96 [1.28–3.03]) and CPR to ROSC ≥ 20 min (OR = 2.13 [1.39–3.23]).Using multinomial regression, an increase in CCI was associated with all modes of in-hospital death, particularly with WLST-related death (RRadj = 2.48 [1.26–4.90], p = 0.01 for CCI = 1–3 and 3.75 [1.85−8.7.58], p < 0.001 for CCI ≥ 4, reference CCI = 0). ConclusionAlteration of chronic health status, as assessed by an elevated CCI, was associated with a higher mortality and a worse neurological outcome in OHCA patients. Presence and burden of comorbidities should be considered in the evaluation of the prognosis in patients admitted in hospital after cardiac arrest.

The Impact of Hyperoxia Treatment on Neurological Outcomes and Mortality in Moderate to Severe Traumatic Brain Injured Patients.

BackgroundTraumatic brain injury is a leading cause of morbidity and mortality worldwide. The relationship between hyperoxia and outcomes in patients with TBI remains controversial. We assessed the effect of persistent hyperoxia on the neurological outcomes and survival of critically ill patients with moderate-severe TBI.MethodThis was a retrospective cohort study of all adults with moderate-severe TBI admitted to the ICU between 1st January 2016 and 31st December 2019 and who required invasive mechanical ventilation. Arterial blood gas data was recorded within the first 3 hours of intubation and then after 6-12 hours and 24-48 hours. The patients were divided into two categories: Group I had a PaO2 < 120mmHg on at least two ABGs undertaken in the first twelve hours post intubation and Group II had a PaO2 ≥ 120mmHg on at least two ABGs in the same period. Multivariable logistic regression was performed to assess predictors of hospital mortality and good neurologic outcome (Glasgow outcome score ≥ 4).ResultsThe study included 309 patients: 54.7% (n=169) in Group I and 45.3% (n=140) in Group II. Hyperoxia was not associated with increased mortality in the ICU (20.1% vs. 17.9%, p=0.62) or hospital (20.7% vs. 17.9%, p=0.53), moreover, the hospital discharge mean (SD) Glasgow Coma Scale (11.0(5.1) vs. 11.2(4.9), p=0.70) and mean (SD) Glasgow Outcome Score (3.1(1.3) vs. 3.1(1.2), p=0.47) were similar. In multivariable logistic regression analysis, persistent hyperoxia was not associated with increased mortality (adjusted odds ratio [aOR] 0.71, 95% CI 0.34-1.35, p=0.29). PaO2 within the first 3 hours was also not associated with mortality: 121-200mmHg: aOR 0.58, 95% CI 0.23-1.49, p=0.26; 201-300mmHg: aOR 0.66, 95% CI 0.27-1.59, p=0.35; 301-400mmHg: aOR 0.85, 95% CI 0.31-2.35, p=0.75 and >400mmHg: aOR 0.51, 95% CI 0.18-1.44, p=0.20; reference: PaO2 60-120mmHg within 3 hours. However, hyperoxia >400mmHg was associated with being less likely to have good neurological (GOS ≥4) outcome on hospital discharge (aOR 0.36, 95% CI 0.13-0.98, p=0.046; reference: PaO2 60-120mmHg within 3 hours.ConclusionIn intubated patients with moderate-severe TBI, hyperoxia in the first 48 hours was not independently associated with hospital mortality. However, PaO2 >400mmHg may be associated with a worse neurological outcome on hospital discharge.

Surgical Evacuation of Intracerebral Hemorrhage: The Potential Importance of Timing.

Surgical Evacuation of Intracerebral Hemorrhage: The Potential Importance of Timing.

Dysnatremia and 6-Month Functional Outcomes in Critically Ill Patients With Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.

To investigate the association between plasma sodium concentrations and 6-month neurologic outcome in critically ill patients with aneurysmal subarachnoid hemorrhage. Prospective cohort study. Eleven ICUs in Australia and New Zealand. Three-hundred fifty-six aneurysmal subarachnoid hemorrhage patients admitted to ICU between March 2016 and June 2018. The exposure variable was daily measured plasma sodium. None. Six-month neurologic outcome as measured by the modified Rankin Scale. A poor outcome was defined as a modified Rankin Scale greater than or equal to 4. The mean age was 57 years (± 12.6 yr), 68% were female, and 32% (n = 113) had a poor outcome. In multivariable analysis, including age, illness severity, and process of care measures as covariates, higher mean sodium concentrations (odds ratio, 1.17; 95% CI, 1.05-1.29), and greater overall variability-as measured by the sd (odds ratio, 1.53; 95% CI, 1.17-1.99)-were associated with a greater likelihood of a poor outcome. Multivariable generalized additive modeling demonstrated, specifically, that a high initial sodium concentration, followed by a gradual decline from day 3 onwards, was also associated with a poor outcome. Finally, greater variability in sodium concentrations was associated with a longer ICU and hospital length of stay: mean ICU length of stay ratio (1.13; 95% CI, 1.07-1.20) and mean hospital length of stay ratio (1.08; 95% CI, 1.01-1.15). In critically ill aneurysmal subarachnoid hemorrhage patients, higher mean sodium concentrations and greater variability were associated with worse neurologic outcomes at 6 months, despite adjustment for known confounders. Interventional studies would be required to demonstrate a causal relationship.

Impact of Total Epinephrine Dose on Long Term Neurological Outcome for Cardiac Arrest Patients: A Cohort Study.

Introduction: Although epinephrine is universally acknowledged to increase return of spontaneous circulation (ROSC) after cardiac arrest, its balanced effects on later outcomes remain uncertain, causing potential harm during post-resuscitation phase. Recent studies have questioned the efficacy and potential deleterious effects of epinephrine on long-term survival and neurological outcomes, despite that the adverse relationship between epinephrine dose and outcome can be partially biased by longer CPR duration and underlying comorbidities. This study explored the long-term effect of epinephrine when used in a cohort of patients that underwent cardiac arrest during cardiopulmonary resuscitation. Methods: The data were originally collected from a retrospective institutional database from January 2007 to December 2015 and are now available on Dryad (via: https://doi.org/10.5061/dryad.qv6fp83). Use of epinephrine was coded by dose (<2 mg, 2 mg, 3–4 mg, ≥5 mg). A favorable neurological outcome was defined using a Cerebral Performance Category (CPC) 1 or 2. The association between epinephrine dosing and 3-months neurological outcome was analyzed by univariate analysis and multivariate logistic regression. Results: Univariate and multivariate analysis demonstrated a negative association between total epinephrine dose and neurological outcome. Of the 373 eligible patients, 92 received less than 2 mg of epinephrine, 60 received 2 mg, 97 received 3–4 mg and 124 received more than 5 mg. Compared to patients who received less than 2 mg of epinephrine, the adjusted odds ratio (OR) of a favorable neurological outcome was 0.8 (95% confidence interval [CI]: 0.38–1.68) for 2 mg of epinephrine, 0.43 (95% confidence interval [CI]: 0.21–0.89) for 3–4 mg of epinephrine and 0.40 (95% confidence interval [CI]: 0.17–0.96) for more than 5 mg of epinephrine. Conclusion: In this cohort of patients who achieved ROSC, total epinephrine dosing during resuscitation was associated with a worse neurological outcome three months after cardiac arrest, after adjusting other confounding factors. Further researches are needed to investigate the long-term effect of epinephrine on cardiac arrest patients.

Characteristics and Outcomes of Left Ventricular-Assist Device-Associated Cerebrovascular Events in Setting of Infectious Intracranial Aneurysms.

Background and purpose: The study aims to identify the characteristics and neurological outcomes of the left ventricular-assist device (LVAD)-associated cerebrovascular events (CVE) and infections, particularly in the setting of infectious intracranial aneurysms (IIA).Methods: A single-center retrospective review of patients having undergone LVAD implantation between 2011 and 2017 was conducted using institutional registries and screened for CVE. Patients with CVE were assessed for concurrent bacteremia; neurovascular imaging was then used to isolate patients with IIA. A review of comorbidities, imaging characteristics, and management were performed to determine predictors of neurological outcomes, as defined by the 90-day modified Rankin scale (mRS) scores.Results: Of the 383 HeartMate II LVAD implantations performed, 43 all-cause stroke events were identified across 35 (9%) patients. The majority of the events were hemorrhagic CVE (n=28) with 21 events complicated by bacteremia. Of patients with hemorrhagic CVE and bacteremia, Staphylococcus aureus (n=10) and Pseudomonas aeruginosa (n= 8) infection were the most frequently associated organisms. Severe disability or death (90-day mRS > 4) was observed in 15 patients (63%). Seven patients had confirmed findings of IIA on diagnostic cerebral angiogram and were associated with distal middle cerebral artery (MCA) territory involvement (n=6; 86%) with concurrent Staphylococcus (n=5, 71%) and/or Pseudomonas (n=4, 57%) infections. Overall, a higher incidence of acute and chronic bacteremia was observed in the hemorrhagic CVE subgroup compared to the ischemic CVE subgroup (74% vs 36% & 71% vs 29%, respectively; p <0.05). Despite endovascular and/or surgical intervention in patients with IIA, four patients failed management and elected for comfort measures.Conclusion: Our results indicate that P. aeruginosa and S. aureus bacteremia are associated with a greater incidence of intracranial hemorrhage and worse neurological outcomes. Future management considerations may include pre-implantation cerebrovascular imaging to assess vascular pathology including prior aneurysms and intracranial atherosclerotic disease burden as a screen for higher-risk patients, as well as more aggressive antibiotic therapy at bacteremia onset.

Thinking fast and slow: lactate and MELD-XI (model for end-stage liver disease excluding INR) are useful for estimating mortality after cardiopulmonary resuscitation.

Intensivists keep getting challenged with prognostication after cardiopulmonary resuscitation (CPR). The model for end-stage liver disease, excluding INR (MELD-XI) Score has proven valuable for assessing illness severity. Serum lactate is a readily available and established indicator of general stress and tissue hypoxia. We aimed to evaluate the prognostic value of MELD-XI combined with serum lactate in patients after CPR. A retrospective analysis on 106 patients after CPR was performed. Multivariable Cox regression was performed to evaluate associations with 30-day mortality and neurological outcome by means of cerebral performance category (CPC). An optimal cut-off was calculated by means of the Youden Index. Patients were then divided into subgroups based on the optimal cut-offs for MELD-XI and serum lactate. MELD-XI and lactate were independently associated with mortality. The respective cut-offs were MELD-XI>12 and lactate ≥2.5 mmol/L. Patients were split into three groups: lactate <2.5 mmol/L and MELD-XI≤12 (low-risk; N.=32), lactate ≥2.5 mmol/L or MELD-XI>12 (medium-risk; N.=39), and lactate ≥2.5 mmol/L and MELD-XI >12 (high-risk; N.=33). The mortality rates were 6%, 26% and 61% in the low, medium and high-risk group. This combined model yielded in the highest predictive abilities (AUC=0.78 95%CI: 0.68-0.85; P=0.03 vs. AUC=0.66 for SOFA Score). Worse neurological outcome (CPC 3 or 4) was more common in the medium and high-risk group (6.25%, 10.3% and 9.1%). The combination of MELD-XI and lactate concentration at ICU admission was superior to the more complex SOFA Score for prediction of mortality after CPR.

Assessment of serum ferritin and thyroid hormones level in acute ischemic stroke and their association with hemorrhagic conversion

Background: Acute ischemic stroke is a significant cause of mortality and the leading cause of long-term disability in the United States. Collective evidence suggests that low T3 levels and serum ferritin levels instantly following acute ischemic stroke are connected with greater stroke sternness, higher death rates, and poor functional outcomes. The aim of the study was to assess the serum ferritin and thyroid hormones level in acute ischemic stroke their association with hemorrhagic conversion.Methods: In this observational study, 60 acute ischemic stroke patients aged ≥ 18 years of both gender who were reported with focal neurological deficit lasting greater than 24 hours were included. Clinical severity of stroke was assessed at admission and on the 7th day using Glasgow coma scale (G.C.S.), serum ferritin level, and thyroid hormones level were measured at admission and on the 7th day in all these subjects.Results: Overall mean age of patients was 56.28±11.45 years with a range of 29-87 years; 61.7% were male patients. Ischemic stroke was found in 55 (91.7%) patients, while 5 (8.3%) patients showed hemorrhagic conversion. Serum Ferritin and T3 level shows a significant association with G.C.S. score (p&lt;0.05). Hemorrhagic Conversion patients were significantly greater in-hospital stay than the acute ischemic stroke group (p&lt;0.05).Conclusions: In our study, it was observed that after acute ischemic stroke high ferritin level and low T3 is associated with worse neurological outcome and linked to the poorer results at hospital discharge.

Systematic review and meta-analysis appraising efficacy and safety of adrenaline for adult cardiopulmonary resuscitation.

There is a beneficial effect of adrenaline during adult cardiopulmonary resuscitation (CPR) from cardiac arrest but there is also uncertainty about its safety and effectiveness. The aim of this study was to evaluate the use of adrenaline versus non-adrenaline CPR. PubMed, ScienceDirect, Embase, CENTRAL (Cochrane Central Register of Controlled Trials) and Google Scholar databases were searched from their inception up to 1st July 2020. Two reviewers independently assessed eligibility and risk of bias, with conflicts resolved by a third reviewer. Risk ratio (RR) or mean difference of groups were calculated using fixed or random-effect models. Nineteen trials were identified. The use of adrenaline during CPR was associated with a significantly higher percentage of return of spontaneous circulation (ROSC) compared to non-adrenaline treatment (20.9% vs. 5.9%; RR = 1.87; 95% confidence interval [CI] 1.37-2.55; p < 0.001). The use of adrenaline in CPR was associated with ROSC at 19.4% and for non-adrenaline treatment - 4.3% (RR = 3.23; 95% CI 1.89-5.53; p < 0.001). Survival to discharge (or 30-day survival) when using adrenaline was 6.8% compared to non-adrenaline treatment (5.5%; RR = 0.99; 95% CI 0.76-1.30; p = 0.97). However, the use of adrenaline was associated with a worse neurological outcome (1.6% vs. 2.2%; RR = 0.57; 95% CI 0.42-0.78; p < 0.001). This review suggests that resuscitation with adrenaline is associated with the ROSC and survival to hospital discharge, but no higher effectiveness was observed at discharge with favorable neurological outcome. The analysis showed higher effectiveness of ROSC and survival to hospital discharge in non-shockable rhythms. But more multicenter randomized controlled trials are needed in the future.

Association Between Ionized Calcium Level and Neurological Outcome in Endovascularly Treated Patients with Spontaneous Subarachnoid Hemorrhage: A Retrospective Cohort Study.

Spontaneous subarachnoid hemorrhage (SSAH) is associated with significant morbidity and mortality. Pathophysiological processes following initial bleeding are complex and not fully understood. In this study, we aimed to determine whether a low level of ionized calcium (Ca++), an essential cofactor in the coagulation cascade and other cellular processes, is associated with adverse neurological outcome, development of early hydrocephalus, and symptomatic vasospasm among patients with SSAH. This was a retrospective single-center cohort study of all patients admitted for SSAH between January 1, 2009, and April 31, 2020. The primary outcome was an unfavorable neurological status at discharge, defined as a modified Rankin Scale score greater than or equal to 3. Secondary outcomes were the development of early hydrocephalus and symptomatic vasospasm. Multivariable logistic regression was performed to determine whether Ca++ was an independent predictor of these outcomes. A total of 255 patients were included in the final analysis. Hypocalcemia, older age, admission Glasgow Coma Scale (GCS) score, and admission Hunt-Hess classification scale (H&H) grades IV and V were independently associated with unfavorable neurological outcome, with adjusted odds ratios (ORs) of 1.93 (95% confidence interval [CI] 1.1-3.4; p = 0.02) for each 0.1mmolL-1 decrease in the Ca++ level, 1.04 (95% CI 1.01-1.08; p = 0.02) for each year increase, 0.82 (95% CI 0.68-0.99; p = 0.04), and 6.29 (95% CI 1.14-34.6; p = 0.03), respectively. Risk factors for the development of hydrocephalus were hypocalcemia and GCS score, with ORs of 1.85 (95% CI 1.26-2.71; p = 0.002) for each 0.1mmol L-1 decrease in the Ca++ level and 0.83 (95% CI 0.73-0.94; p = 0.005), respectively. Ca++ was not associated with symptomatic vasospasm (OR 1.04 [95% CI 0.76-1.41]; p = 0.81). Among patients with admission H&H grade I-III bleeding, hypocalcemia was independently associated with unfavorable neurological outcome at discharge, with an adjusted OR of 1.99 (95% CI 1.03-3.84; p = 0.04) for each 0.1mmol L-1 decrease in the Ca++ level. Hypocalcemia was also an independent risk factor for the development of early hydrocephalus, with an adjusted OR of 2.95 (95% CI 1.49-5.84; p = 0.002) for each 0.1mmol L-1 decrease in the Ca++ level. Ca++ was not associated with symptomatic vasospasm. No association was found between Ca++ and predefined outcomes among patients with admission H&H grade IV and V bleeding. Our study shows that hypocalcemia is associated with worse neurological outcome at discharge and development of early hydrocephalus in endovascularly treated patients with SSAH. Potential mechanisms include calcium-induced coagulopathy and higher blood pressure. Trials are needed to assess whether correction of hypocalcemia will lead to improved outcomes.

Adrenaline to improve survival in out-of-hospital cardiac arrest: the PARAMEDIC2 RCT.

Adrenaline has been used as a treatment for cardiac arrest for many years, despite uncertainty about its effects on long-term outcomes and concerns that it may cause worse neurological outcomes. The objectives were to evaluate the effects of adrenaline on survival and neurological outcomes, and to assess the cost-effectiveness of adrenaline use. This was a pragmatic, randomised, allocation-concealed, placebo-controlled, parallel-group superiority trial and economic evaluation. Costs are expressed in Great British pounds and reported in 2016/17 prices. This trial was set in five NHS ambulance services in England and Wales. Adults treated for an out-of-hospital cardiac arrest were included. Patients were ineligible if they were pregnant, if they were aged < 16 years, if the cardiac arrest had been caused by anaphylaxis or life-threatening asthma, or if adrenaline had already been given. Participants were randomised to either adrenaline (1 mg) or placebo in a 1 : 1 allocation ratio by the opening of allocation-concealed treatment packs. The primary outcome was survival to 30 days. The secondary outcomes were survival to hospital admission, survival to hospital discharge, survival at 3, 6 and 12 months, neurological outcomes and health-related quality of life through to 6 months. The economic evaluation assessed the incremental cost per quality-adjusted life-year gained from the perspective of the NHS and Personal Social Services. Participants, clinical teams and those assessing patient outcomes were masked to the treatment allocation. From December 2014 to October 2017, 8014 participants were assigned to the adrenaline (n = 4015) or to the placebo (n = 3999) arm. At 30 days, 130 out of 4012 participants (3.2%) in the adrenaline arm and 94 out of 3995 (2.4%) in the placebo arm were alive (adjusted odds ratio for survival 1.47, 95% confidence interval 1.09 to 1.97). For secondary outcomes, survival to hospital admission was higher for those receiving adrenaline than for those receiving placebo (23.6% vs. 8.0%; adjusted odds ratio 3.83, 95% confidence interval 3.30 to 4.43). The rate of favourable neurological outcome at hospital discharge was not significantly different between the arms (2.2% vs. 1.9%; adjusted odds ratio 1.19, 95% confidence interval 0.85 to 1.68). The pattern of improved survival but no significant improvement in neurological outcomes continued through to 6 months. By 12 months, survival in the adrenaline arm was 2.7%, compared with 2.0% in the placebo arm (adjusted odds ratio 1.38, 95% confidence interval 1.00 to 1.92). An adjusted subgroup analysis did not identify significant interactions. The incremental cost-effectiveness ratio for adrenaline was estimated at £1,693,003 per quality-adjusted life-year gained over the first 6 months after the cardiac arrest event and £81,070 per quality-adjusted life-year gained over the lifetime of survivors. Additional economic analyses estimated incremental cost-effectiveness ratios for adrenaline at £982,880 per percentage point increase in overall survival and £377,232 per percentage point increase in neurological outcomes over the first 6 months after the cardiac arrest. The estimate for survival with a favourable neurological outcome is imprecise because of the small numbers of patients surviving with a good outcome. Adrenaline improved long-term survival, but there was no evidence that it significantly improved neurological outcomes. The incremental cost-effectiveness ratio per quality-adjusted life-year exceeds the threshold of £20,000-30,000 per quality-adjusted life-year usually supported by the NHS. Further research is required to better understand patients' preferences in relation to survival and neurological outcomes after out-of-hospital cardiac arrest and to aid interpretation of the trial findings from a patient and public perspective. Current Controlled Trials ISRCTN73485024 and EudraCT 2014-000792-11. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 25. See the NIHR Journals Library website for further project information.

Decreased Superoxide Dismutase Concentrations (SOD) in Plasma and CSF and Increased Circulating Total Antioxidant Capacity (TAC) Are Associated with Unfavorable Neurological Outcome after Aneurysmal Subarachnoid Hemorrhage.

Background: Subarachnoid hemorrhage (SAH) is a devastating disease with high morbidity and mortality. Hypoxia-induced changes and hemoglobin accumulation within the subarachnoid space are thought to lead to oxidative stress, early brain injury, and delayed vasospasm. This study aimed to evaluate the antioxidant status and its impact on neurological outcome in patients with aneurysmal SAH. Methods: In this prospective observational study, 29 patients with aneurysmal SAH were included (mean age 54.7 ± 12.4). Blood and cerebrospinal fluid (CSF) samples were collected on days (d) 1, 3, and 7. In addition, 29 patients without intracranial hemorrhage served as controls. The antioxidant system was analyzed by glutathione peroxidase (GSH-Px; U/L) and total and free glutathione-sulfhydryl (GSH; mg/L) in the plasma. Superoxide dismutase (SOD, U/mL) and total antioxidant capacity (TAC, µmol/L) were measured in the serum and CSF. Clinical data were compiled on admission (Hunt and Hess grade, Fisher grade, and GCS). Neurological and cognitive outcome (modified Rankin scale (mRS), Glasgow Outcome Scale Extended (GOSE) and Montreal Cognitive Assessment (MoCA)) was assessed after 6 weeks (6 w) and 6 months (6 m). Results: Plasma levels of SOD increased from day 1 to 7 after SAH (d1: 1.22 ± 0.36 U/L; d3: 1.25 ± 0.33 U/L, p = 0.99; d7: 1.52 ± 0.4 U/L, p = 0.019) and were significantly higher compared to controls (1.11 ± 0.27 U/L) at day 7 (p < 0.001). Concordantly, CSF levels of SOD increased from day 1 to 7 after SAH (d1: 1.22 ± 0.41 U/L; d3: 1.77 ± 0.73 U/L, p = 0.10; d7: 2.37 ± 1.29 U/L, p < 0.0001) without becoming significantly different compared to controls (1.74 ± 0.8 U/L, p = 0.09). Mean plasma TAC at day 1 (d1: 77.87 ± 49.72 µmol/L) was not statistically different compared to controls (46.74 ± 32.42 µmol/L, p = 0.25). TAC remained unchanged from day 1 to 7 (d3: 92.64 ± 68.58 µmol/L, p = 0.86; d7: 74.07 ± 54.95 µmol/L, p = 0.8) in plasma. TAC in CSF steeply declined from day 1 to 7 in patients with SAH becoming significantly different from controls at days 3 and 7 (d3: 177.3 ± 108.7 µmol/L, p = 0.0046; d7: 85.35 ± 103.9 µmol/L, p < 0.0001). Decreased SOD levels in plasma and CSF are associated with a worse neurological outcome 6 weeks (mRS: CSF p = 0.0001; plasma p = 0.027/GOSE: CSF p = 0.001; plasma p = 0.001) and 6 months (mRS: CSF p = 0.001; plasma p = 0.09/GOSE: CSF p = 0.001; plasma p = 0.001) after SAH. Increased plasma TAC correlated with a worse neurological outcome 6 weeks (mRS: p = 0.001/GOSE p = 0.001) and 6 months (mRS p = 0.001/GOSE p = 0.001) after SAH. Conclusion: In our study, a reduction in the antioxidative enzyme SOD and elevated TAC were associated with a poorer neurological outcome reflected by mRS and GOSE at 6 weeks and 6 months after SAH. A lower initial SOD CSF concentration was associated with the late deterioration of cognitive ability. These findings support the mounting evidence of the role of oxidative stress in early brain injury formation and unfavorable outcome after SAH.

Bilateral evacuation of bilateral non-acute subdural hematomas - evaluation of postoperative outcomes and complications.

Bilateral finding of non-acute subdural hematomas (NASH) is less common compared to unilateral occurrence. The aim of this study was to evaluate results of surgical treatment of bilaterally treated bilateral NASH. Retrospective analysis of patients, who underwent bilateral surgical evacuation of NASH (2014-2020). This study was conducted to determine the association between the incidence of postoperative complications and outcome, hematoma recurrence and selected risk factors (including volumetric parameters). Correlations between variables were assessed by using Spearman's correlation. Chi-squared test, Student's t-test (unpaired and paired) and one-way ANOVA were used for univariate analysis. Our study included 29 patients with bilateral NASH who underwent bilateral surgical hematoma evacuation. The laminar hematoma type was associated with higher hematoma recurrence rate (p=0.032) and worse clinical outcome (p=0.043). Larger PHV was significantly associated with larger PV after surgery and worse neurological outcome. Larger PHV, PHCV and PV were significantly associated with higher incidence of NASH recurrence (p=0.0008, p=0.0007 and p=0.00006). The laminar hematoma type and larger PHV were significant risk factors for the recurrence of bilateral NASH and worse neurological outcome. Larger PHCV and PV were significantly associated with hematoma recurrence (Tab. 7, Fig. 3, Ref. 24).

Vertebral Artery Dissections With Concurrent Intracranial Hemorrhage: A Case Series of 13 Patients Among a Cohort of 301

Vertebral artery dissections (VADs) are a rare cause of ischemic stroke that can occasionally lead to intracranial hemorrhage (ICH). This study aims to identify differences in predisposing factors, event characteristics, and outcomes between patients with only a VAD and patients with VAD and concomitant ICH. We conducted a retrospective chart review of 301 patients who presented with VADs at our institution from 2004-2018. A total of 13 patients were identified with VAD and concomitant ICH. Data were collected on demographics, event characteristics, treatments, and neurologic outcomes, measured using the modified Rankin Scale (mRS). VAD+ICH and VAD-only groups were similar in terms of age, sex, and recorded comorbidities. Additionally, etiology of the dissections did not seem to vary between groups (P= 0.6), even when selecting for traumatic causes such as motor vehicle accidents (P=0.22) and violence (P= 0.25). Concomitant strokes and aneurysms/pseudoaneurysms occurred in similar proportions as well, but cervical fractures were more common in the VAD+ICH group (P= 0.003). Using the mRS as a measure of neurological outcome, we found that the VAD+ICH group had worse neurologic function at discharge, 3-month follow-up, and last follow-up (P<0.001). Patients who experienced an ICH in addition to a VAD did not have any identifiable risk factors. Cervical spine fractures were more common in patients with VAD and ICH. VAD patients with a concomitant ICH have worse neurologic outcomes than patients with only aVAD.

Heart Rate and Neurological Outcomes in Patients Undergoing Targeted Temperature Management

There is a paucity of data evaluating the impact of heart rate (HR) during Targeted Temperature Management (TTM) and neurologic outcomes. Current resuscitation guidelines do not specify a HR goal during TTM. We sought to determine the relationship between HR and neurologic outcomes in a single-center registry dataset. We retrospectively studied 432 consecutive patients who completed TTM (33°C) after cardiac arrest from 2008 to 2017. We evaluated the relationship between neurologic outcomes and HR during TTM. Pittsburgh Cerebral Performance Categories (CPC) at discharge were used to determine neurological recovery. Statistical analysis included chi square, Student's t-test and Mann-Whitney U. A logistic regression model was created to evaluate the strength of contribution of selected variables on the outcome of interest. Approximately 94,000 HR data points from 432 patients were retrospectively analyzed; the mean HR was 82.17 bpm over the duration of TTM. Favorable neurological outcomes were seen in 160 (37%) patients. The mean HR in the patients with a favorable outcome was lower than the mean HR of those with an unfavorable outcome (79.98 bpm vs 85.67 bpm p < 0.001). Patients with an average HR of 60-91 bpm were 2.4 times more likely to have a favorable neurological outcome compared to than HR's < 60 or > 91 (odds ratio [OR] = 2.36, 95% confidence interval [CI] 1.61-3.46, p < 0.001). Specifically, mean HR's in the 73-82 bpm range had the greatest rate of favorable outcomes (OR 3.56, 95% CI 1.95-6.50), p < 0.001. Administration of epinephrine, a history of diabetes mellitus and hypertension all were associated with worse neurological outcomes independent of HR. During TTM, mean HRs between 60-91 showed a positive association with favorable outcomes. It is unclear whether a specific HR should be targeted during TTM or if heart rates between 60-91 bpm might be a sign of less neurological damage.

Intracranial Pressure Monitors are Associated with Worse Neurologic Outcome after Spontaneous Intracranial Hemorrhage

Intracranial Pressure Monitors are Associated with Worse Neurologic Outcome after Spontaneous Intracranial Hemorrhage

Abstract 232: Delayed Administration of Epinephrine is Associated with Worse Neurological Outcomes in Patients with Out-of-hospital Cardiac Arrest and Initial Pulseless Electrical Activity

Background: Delayed administration of epinephrine has been proven to worsen the neurological outcomes of patients with out-of-hospital cardiac arrest (OHCA) and initial shockable rhythm. We aimed to investigate whether delayed administration of epinephrine might also worsen the neurological outcomes of patients with witnessed OHCA and initial pulseless electrical activity (PEA). Methods: The Japanese Association for Acute Medicine - out-of-hospital cardiac arrest (JAAM-OHCA) Registry is a multicenter, prospective, observational registry including 34,754 OHCA patients between 2014 and 2017. The present study assessed the impact of the time to epinephrine administration on neurological outcomes in patients with witnessed non-traumatic OHCA with initial rhythm of PEA. The primary outcome was defined as Cerebral Performance Categories (CPC) Scale 1-2 at 30 days after OHCA. The association between the odds ratio for the primary outcome and the time from witnessed OHCA to epinephrine administration was assessed with a restricted cubic spline analysis. Results: Out of 34,754 patients with OHCA, 3,050 patients with OHCA and initial PEA who received epinephrine were included in the present study. Mean age was 73.7 years and 1836 (60.2%) was male. After adjusting for potential confounders, the time from witnessed OHCA to epinephrine administration was associated with lower likelihood of favorable neurological outcomes (odds ratio [OR] 0.92; 95% confidence interval [CI] 0.89-0.96; P&amp;lt;0.001). The restricted cubic spline analysis demonstrated that delayed epinephrine administration could decrease the likelihood of a favorable neurological outcome; this was significant within the first 10 minutes. Conclusions: Delayed administration of epinephrine was associated with worse neurological outcomes in patients with witnessed OHCA patients with initial PEA.

Abstract 274: Drugs and Cardiac Arrest: Suffocate the Brain, Spare the Body?

Background: Nearly 70,000 people die of a drug overdose every year. Yet, how drug induced cardiac arrests differ from presumed cardiac etiology cardiac arrests is not well described. In animal models, asphyxial arrests resemble drug induced arrests, demonstrating better hemodynamic profiles yet worse neurologic recovery. Theoretically, this is caused by hypoxemic but preserved perfusion prior to ultimate arrest. But, this has not been studied in humans. We hypothesize that drug induced cardiac arrests will have higher incidence of return of spontaneous circulation (ROSC) in all comers, yet worse neurologic recovery among hospitalized patients. Methods: From a large institutional dataset capturing all patients with out-of-hospital cardiac arrests admitted from 2011 to 2019, we assess the prevalence and outcomes of cardiac arrests, by drug-use status. Patients were excluded if the arrest was trauma induced, occurred in an extended care facility/nursing home, or if treatment was initiated at another medical center. The primary outcome was ROSC in all comers, and the secondary outcome was favorable neurologic function among those surviving to admission. Multivariable logistic regression was used to assess factors associated with differences in outcomes, accounting for traditional cardiac risk factors and arrest characteristics. Results: In total, 436 patients (57±10 years, 31.7% female, 58.5% non-white, 49.3% hypertensive, 28.4% diabetics, and 21.1% preceding coronary disease) were identified, including 94 (21.6%) with drug induced cardiac arrest. Of that total group 101 (23.2%) survived, to admission, 26.6% of the drug induced group and 22.2% of the presumed cardiac cohort, demonstrating no difference in ROSC (P=0.32). Among those that survived to admission, 8% (2/25) of the drug induced group had a favorable neurologic outcome, compared to 29.0% (22/76) of the cardiac induced group (P= 0.03). Following adjustment, the presence of presenting drug induced cardiac arrest remained associated with lower rates of neurologic recovery [OR 7.3 (1.03-51.6) P= 0.04]. There was no difference in survival to discharge. Conclusion: Drug induced cardiac arrest is associated with worse neurologic outcomes than presumed cardiac etiology cardiac arrests.