Medical Treatment Failure for Symptomatic Vasospasm After Subarachnoid Hemorrhage Threatens Long-Term Outcome.

Background and Purpose- Symptomatic vasospasm is a common cause of morbidity and mortality after subarachnoid hemorrhage. We sought to identify predictors and the long-term impact of treatment failure with hypertensive therapy for symptomatic vasospasm. Methods- We performed a retrospective analysis of 1520 subarachnoid hemorrhage patients prospectively enrolled in the Columbia University SAH Outcomes Project between August 1996 and August 2012. One hundred ninety-eight symptomatic vasospasm patients were treated with vasopressors to raise arterial blood pressure, with and without volume expansion. Treatment response, defined as complete or near-complete resolution of the initial neurological deficit, was adjudicated in weekly meetings of the study team based on serial clinical examination after hypertensive treatment. Outcome was evaluated at 1 year with the modified Rankin Scale. Results- Twenty-one percent of the 198 patients who received hypertensive therapy did not respond to treatment. Treatment failure was associated with an increased risk of death or severe disability at 1 year (modified Rankin Scale score of 4-6; 62% versus 25%; P<0.001). Failure of medical therapy was also associated with an admission troponin I level >0.3 µg/L (64% versus 28%; P=0.001), aneurysm coiling (43% versus 20%; P=0.004), and involvement of >1 symptomatic vascular territory at onset (39% versus 22%; P=0.02). In multivariable analysis, treatment failure was independently associated only with troponin I elevation (adjusted odds ratio, 4.30; 95% CI, 1.69-11.09; P=0.002). Conclusions- Failure to respond to induced hypertension for symptomatic vasospasm threatens 1-year outcome. Subarachnoid hemorrhage patients with symptomatic vasospasm who have elevated initial troponin I levels, indicative of neurogenic cardiac injury, are at twice the risk of medical treatment failure. Expedited endovascular therapy should be considered in these patients.

Predicting delayed cerebral ischemia after subarachnoid hemorrhage using physiological time series data.

To develop and validate a prediction model for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) using a temporal unsupervised feature engineering approach, demonstrating improved precision over standard features. 488 consecutive SAH admissions from 2006 to 2014 to a tertiary care hospital were included. Models were trained on 80%, while 20% were set aside for validation testing. Baseline information and standard grading scales were evaluated: age, sex, Hunt Hess grade, modified Fisher Scale (mFS), and Glasgow Coma Scale (GCS). An unsupervised approach applying random kernels was used to extract features from physiological time series (systolic and diastolic blood pressure, heart rate, respiratory rate, and oxygen saturation). Classifiers (Partial Least Squares, linear and kernel Support Vector Machines) were trained on feature subsets of the derivation dataset. Models were applied to the validation dataset. The performances of the best classifiers on the validation dataset are reported by feature subset. Standard grading scale (mFS): AUC 0.58. Combined demographics and grading scales: AUC 0.60. Random kernel derived physiologic features: AUC 0.74. Combined baseline and physiologic features with redundant feature reduction: AUC 0.77. Current DCI prediction tools rely on admission imaging and are advantageously simple to employ. However, using an agnostic and computationally inexpensive learning approach for high-frequency physiologic time series data, we demonstrated that our models achieve higher classification accuracy.

Duration of Agitation, Fluctuations of Consciousness, and Associations with Outcome in Patients with Subarachnoid Hemorrhage.

BACKGROUND: Agitation is common after subarachnoid hemorrhage (SAH) and may be independently associated with outcomes. We sought to determine whether the duration of agitation and fluctuating consciousness were also associated with outcomes in patients with SAH. METHODS: We identified all patients with positive Richmond Agitation Sedation Scale (RASS) scores from a prospective observational cohort of patients with SAH from 2011 to 2015. Total duration of agitation was extrapolated for each patient using available RASS scores, and 24-h mean and standard deviation (SD) of RASS scores were calculated for each patient. We also calculated each patient's duration of substantial fluctuation of consciousness, defined as the number of days with 24-h RASS SD > 1. Patients were stratified by 3-month outcome using the modified Rankin scale, and associations with outcome were assessed via logistic regression. RESULTS: There were 98 patients with at least one positive RASS score, with median total duration of agitation 8 h (interquartile range [IQR] 4-18), and median duration of substantially fluctuating consciousness 2 days (IQR 1-3). Unfavorable 3-month outcome was significantly associated with a longer duration of fluctuating consciousness (odds ratio [OR] per day, 1.51; 95% confidence interval [CI], 1.04-2.20; p = 0.031), but a briefer duration of agitation (OR per hour, 0.94; 95% CI, 0.89-0.99; p = 0.031). CONCLUSION: Though a longer duration of fluctuating consciousness was associated with worse outcomes in our cohort, total duration of agitation was not, and may have had the opposite effect. Our findings should therefore challenge the intensity with which agitation is often treated in SAH patients.

Primary Intracerebral Hemorrhage: A Closer Look at Hypertension and Cerebral Amyloid Angiopathy.

BACKGROUND/PURPOSE: Primary intracerebral hemorrhage (ICH) studies often use hematoma location rather than ICH etiologies when assessing outcome. Characterizing ICH using hematoma location is effective/reproducible, but may miss heterogeneity among these ICH locations, particularly lobar ICH where competing primary ICH etiologies are possible. We subsequently investigated baseline characteristics/outcome differences of spontaneous, primary ICH by their etiologies: cerebral amyloid angiopathy (CAA) and hypertension. METHODS: Primary ICH clinical/outcomes data were prospectively collected between 2009 and 2015. Modified Boston criteria were used to identify "probable/definite" and "possible" CAA-ICH, which were evaluated separately. SMASH-U criteria were used to identify hypertension ICH. Medication and systemic disease coagulopathy ICH were excluded. Baseline characteristics/outcomes among "probable/definite" CAA-ICH, "possible" CAA-ICH, and hypertension ICH were compared using logistic regression. Mortality models using ICH etiologies compared to hematoma location as predictor variables were assessed. RESULTS: Two hundred and four hypertension ICHs, 55 "probable/definite" CAA-ICHs, and 46 "possible" CAA-ICHs were identified. Despite older age and larger ICH volumes, lower hospital mortality was seen in "probable/definite" CAA-ICH versus hypertension ICH (OR 0.2; 95% CI 0.05-0.8; p = 0.02) after adjusting for female gender, components of ICH score, and EVD placement. There were no mortality differences between "possible" CAA-ICH and hypertension ICH. However, lower hospital mortality was seen in "probable/definite" versus "possible" CAA-ICH (OR 0.2; 95% CI 0.04-0.7; p = 0.02). When using ICH etiology rather than hematoma location, hospital mortality models significantly improved (χ2: [df = 2, N = 305] = 6.2; p = 0.01). CONCLUSIONS: Further investigation is required to confirm the mortality heterogeneity seen within our primary ICH cohort. Hematoma location may play a role for these findings, but the mortality differences seen among lobar ICH using CAA-ICH subtypes and a failure to identify mortality differences between "possible" CAA-ICH and hypertension ICH suggest the limitations of accounting for hematoma location alone.

Prognostication of long-term outcomes after subarachnoid hemorrhage: The FRESH score.

OBJECTIVE: To create a multidimensional tool to prognosticate long-term functional, cognitive, and quality of life outcomes after spontaneous subarachnoid hemorrhage (SAH) using data up to 48 hours after admission. METHODS: Data were prospectively collected for 1,619 consecutive patients enrolled in the SAH outcome project July 1996 to March 2014. Linear models (LMs) were applied to identify factors associated with outcome in 1,526 patients with complete data. Twelve-month functional, cognitive, and quality of life outcomes were measured using the modified Rankin scale (mRS), Telephone Interview for Cognitive Status, and Sickness Impact Profile. Based on the LM residuals, we constructed the FRESH score (Functional Recovery Expected after Subarachnoid Hemorrhage). Score performance, discrimination, and internal validity were tested using the area under the receiver operating characteristic curve (AUC), Nagelkerke and Cox/Snell R(2) , and bootstrapping. For external validation, we used a control population of SAH patients from the CONSCIOUS-1 study (n = 413). RESULTS: The FRESH score was composed of Hunt & Hess and APACHE-II physiologic scores on admission, age, and aneurysmal rebleed within 48 hours. Separate scores to prognosticate 1-year cognition (FRESH-cog) and quality of life (FRESH-quol) were developed controlling for education and premorbid disability. Poor functional outcome (mRS = 4-6) for score levels 1 through 9 respectively was present in 3, 6, 12, 38, 61, 83, 92, 98, and 100% at 1-year follow-up. Performance of FRESH (AUC = 0.90), FRESH-cog (AUC = 0.80), and FRESH-quol (AUC = 0.78) was high. External validation of our cohort using mRS as endpoint showed satisfactory results (AUC = 0.77). To allow for convenient score calculation, we built a smartphone app available for free download. INTERPRETATION: FRESH is the first clinical tool to prognosticate long-term outcome after spontaneous SAH in a multidimensional manner. Ann Neurol 2016;80:46-58.

Agitation After Subarachnoid Hemorrhage: A Frequent Omen of Hospital Complications Associated with Worse Outcomes.

BACKGROUND: Agitated delirium is frequent following acute brain injury, but data are limited in patients with subarachnoid hemorrhage (SAH). We examined incidence, risk factors, and consequences of agitation in these patients in a single-center retrospective study. METHODS: We identified all patients treated with antipsychotics or dexmedetomidine from a prospective observational cohort of patients with spontaneous SAH. Agitation was confirmed by chart review. Outcomes were assessed at 12 months using the modified Rankin Scale (mRS), Telephone Interview for Cognitive Status (TICS), and Lawton IADL (Instrumental Activities of Daily Living) scores. Independent predictors were identified using logistic regression. RESULTS: From 309 SAH patients admitted between January 2011 and December 2015, 52 (17 %) developed agitation, frequently in the first 72 h (50 %) and in patients with Hunt-Hess grades 3-4 (12 % of grades 1-2, 28 % of grades 3-4, 8 % of grade 5). There was also a significant association between agitation and a history of cocaine use or prior psychiatric diagnosis. Agitated patients were more likely to develop multiple hospital complications; and in half of these patients, complications were diagnosed within 24 h of agitation onset. Agitation was associated with IADL impairment at 12 months (Lawton >8; p = 0.03, OR 2.7, 95 % CI, 1.1-6.8) in non-comatose patients (Hunt-Hess 1-4), but not with functional outcome (mRS >3), cognitive impairment (TICS ≤30), or ICU/hospital length of stay after controlling for other predictors. CONCLUSION: Agitation occurs frequently after SAH, especially in non-comatose patients with higher clinical grades. It is associated with the development of multiple hospital complications and may have an independent impact on long-term outcomes.

Assessment of Noninvasive Regional Brain Oximetry in Posterior Reversible Encephalopathy Syndrome and Reversible Cerebral Vasoconstriction Syndrome.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) leads to small- and large-vessel circulatory dysfunction. While aggressive lowering of elevated blood pressure is the usual treatment for PRES, excessive blood pressure reduction may lead to ischemia or infarction, particularly when PRES is accompanied by reversible cerebral vasoconstriction syndrome (RCVS). Regional cerebral oximetry using near-infrared spectroscopy is a noninvasive modality that is commonly used intraoperatively and in intensive care settings to monitor regional cerebral oxygenation (rSO2) and may be useful in guiding treatment in select cases of PRES and RCVS. RESULTS: We report a case of a patient with PRES complicated by infarction and RCVS where the optimal blood pressure management was unclear. A decision was made to decrease blood pressure which resulted in an improved neurological examination and increase in rSO2 from 40% to 55% in at-risk brain. Infarcted brain as determined by diffusion-weighted magnetic resonance imaging and computed tomography perfusion imaging showed no change in rSO2 during the same time period. Furthermore, there was a qualitative change in the rSO2-mean arterial pressure (MAP) relationship, suggesting an alteration in cerebrovascular autoregulation as a result of lowering blood pressure. CONCLUSIONS: Regional cerebral oximetry can provide valuable diagnostic feedback in complicated cases of PRES and RCVS.

The Effect of Packed Red Blood Cell Transfusion on Cerebral Oxygenation and Metabolism After Subarachnoid Hemorrhage.

BACKGROUND: Anemia adversely affects cerebral oxygenation and metabolism after subarachnoid hemorrhage (SAH) and is also associated with poor outcome. There is limited evidence to support the use of packed red blood cell (PRBC) transfusion to optimize brain homeostasis after SAH. The aim of this study was to investigate the effect of transfusion on cerebral oxygenation and metabolism in patients with SAH. METHODS: This was a prospective observational study in a neurological intensive care unit of a university hospital. Nineteen transfusions were studied in 15 consecutive patients with SAH that underwent multimodality monitoring (intracranial pressure, brain tissue oxygen, and cerebral microdialysis). Data were collected at baseline and for 12 h after transfusion. The relationship between hemoglobin (Hb) change and lactate/pyruvate ratio (LPR) orbrain tissue oxygen (PbtO2) was tested using univariate and multivariable analyses. RESULTS: PRBC transfusion was administered on the median post-bleed day 8. The average Hb concentration at baseline was 8.1 g/dL and increased by 2.2 g/dL after transfusion. PbtO2 increased between hours 2 and 4 post-transfusion and this increase was maintained until hour 10. LPR did not change significantly during the 12-h monitoring period. After adjusting for SpO2, cerebral perfusion pressure, and LPR, the change in Hb concentration was independently and positively associated with a change in PbtO2 (adjusted b estimate = 1.39 [95% confidence interval 0.09-2.69]; P = 0.04). No relationship between the change in Hb concentration and LPR was found. CONCLUSIONS: PRBC transfusion resulted in PbtO2 improvement without a clear effect on cerebral metabolism prior to SAH.

Assessment of satisfaction with care and decision-making among English and Spanish-speaking family members of neuroscience ICU patients.

BACKGROUND: Patients' and family members' experiences of hospital care are important indicators of quality. "Black, Asian, and Hispanic patients are more at risk than White patients for decreased satisfaction with care." In addition, of any of these groups, Hispanic patients were most likely to report a lack of patient-centered care. In the intensive care setting, (ICU) previous research has indicated that the needs and satisfaction of family members of neurological ICU patients are different from those of family members of other types of ICU patients. PURPOSE: The purpose of this study was to determine if there were any differences between English-speaking and Spanish-speaking family members of patients in a neurological ICU. METHODS: This study was a single center prospective study conducted over a 10-month period from April 2013 to February 2014 in the 18-bed neuroscience ICU of a large, urban, academic medical center. The Family Satisfaction with ICU (FS-ICU) questionnaire was used; it provides an overall score and has two factors: satisfaction with care and satisfaction with decision-making. RESULTS: There was no statistical significance between the two groups in overall satisfaction or in satisfaction with care, however Spanish-speakers (n=22) were significantly less satisfied (p=.04) than English-speakers (n=50) with decision-making. There were three other discreet variables in which Spanish-speakers were also less satisfied: (a) management of patients' pain (OR 3.16, 95% CI [1.12, 8.9]) (b) management of patients' breathlessness (OR 3.5, 95% CI [1.23, 9.96]) as well as (c) ease of getting information (OR 3.25, 95% CI [1.09, 9.64]). CONCLUSION: Using a standardized survey it was found that Spanish-speakers were statistically less satisfied with decision-making than English-speakers. Additionally, Spanish-speakers were statistically less satisfied with management of patients' pain and breathlessness and ease of getting information. Based on these findings, increased vigilance is recommended regarding decision-making processes of Hispanic-families, especially with regard to provision of information.

Nonconvulsive seizures in subarachnoid hemorrhage link inflammation and outcome.

OBJECTIVE: Nonconvulsive seizures (NCSz) are frequent following acute brain injury and have been implicated as a cause of secondary brain injury, but mechanisms that cause NCSz are controversial. Proinflammatory states are common after many brain injuries, and inflammation-mediated changes in blood-brain barrier permeability have been experimentally linked to seizures. METHODS: In this prospective observational study of aneurysmal subarachnoid hemorrhage (SAH) patients, we explored the link between the inflammatory response following SAH and in-hospital NCSz studying clinical (systemic inflammatory response syndrome [SIRS]) and laboratory (tumor necrosis factor receptor 1 [TNF-R1], high-sensitivity C-reactive protein [hsCRP]) markers of inflammation. Logistic regression, Cox proportional hazards regression, and mediation analyses were performed to investigate temporal and causal relationships. RESULTS: Among 479 SAH patients, 53 (11%) had in-hospital NCSz. Patients with in-hospital NCSz had a more pronounced SIRS response (odds ratio [OR]=1.9 per point increase in SIRS, 95% confidence interval [CI]=1.3-2.9), inflammatory surges were more likely immediately preceding NCSz onset, and the negative impact of SIRS on functional outcome at 3 months was mediated in part through in-hospital NCSz. In a subset with inflammatory serum biomarkers, we confirmed these findings linking higher serum TNF-R1 and hsCRP to in-hospital NCSz (OR=1.2 per 20-point hsCRP increase, 95% CI=1.1-1.4; OR=2.5 per 100-point TNF-R1 increase, 95% CI=2.1-2.9). The association of inflammatory biomarkers with poor outcome was mediated in part through NCSz. INTERPRETATION: In-hospital NCSz were independently associated with a proinflammatory state following SAH as reflected in clinical symptoms and serum biomarkers of inflammation. Our findings suggest that inflammation following SAH is associated with poor outcome and that this effect is at least in part mediated through in-hospital NCSz.

Subarachnoid hemorrhage: who dies, and why?

INTRODUCTION: Subarachnoid hemorrhage (SAH) is a devastating form of stroke. Causes and mechanisms of in-hospital death after SAH in the modern era of neurocritical care remain incompletely understood. METHODS: We studied 1200 consecutive SAH patients prospectively enrolled in the Columbia University SAH Outcomes Project between July 1996 and January 2009. Analysis was performed to identify predictors of in-hospital mortality. RESULTS: In-hospital mortality was 18% (216/1200): 3% for Hunt-Hess grade 1 or 2, 9% for grade 3, 24% for grade 4, and 71% for grade 5. The most common adjudicated primary causes of death or neurological devastation leading to withdrawal of support were direct effects of the primary hemorrhage (55%), aneurysm rebleeding (17%), and medical complications (15%). Among those who died, brain death was declared in 42%, 50% were do-not-resuscitate at the time of cardiac death (86% of whom had life support actively withdrawn), and 8% died despite full support. Admission predictors of mortality were age, loss of consciousness at ictus, admission Glasgow Coma Scale score, large aneurysm size, Acute Physiology and Chronic Health Evaluation II (APACHE II) physiologic subscore, and Modified Fisher Scale score. Hospital complications that further increased the risk of dying in multivariable analysis included rebleeding, global cerebral edema, hypernatremia, clinical signs of brain stem herniation, hypotension of less than 90 mm Hg treated with pressors, pulmonary edema, myocardial ischemia, and hepatic failure. Delayed cerebral ischemia, defined as deterioration or infarction from vasospasm, did not predict mortality. CONCLUSION: Strategies directed toward minimizing early brain injury and aneurysm rebleeding, along with prevention and treatment of medical complication, hold the best promise for further reducing mortality after SAH.

Data collection and interpretation.

Patient monitoring is routinely performed in all patients who receive neurocritical care. The combined use of monitors, including the neurologic examination, laboratory analysis, imaging studies, and physiological parameters, is common in a platform called multi-modality monitoring (MMM). However, the full potential of MMM is only beginning to be realized since for the most part, decision making historically has focused on individual aspects of physiology in a largely threshold-based manner. The use of MMM now is being facilitated by the evolution of bio-informatics in critical care including developing techniques to acquire, store, retrieve, and display integrated data and new analytic techniques for optimal clinical decision making. In this review, we will discuss the crucial initial steps toward data and information management, which in this emerging era of data-intensive science is already shifting concepts of care for acute brain injury and has the potential to both reshape how we do research and enhance cost-effective clinical care.

Ethnic disparities in end-of-life care after subarachnoid hemorrhage.

BACKGROUND: It is common for patients who die from subarachnoid hemorrhage to have a focus on comfort measures at the end of life. The potential role of ethnicity in end-of-life decisions after brain injury has not been extensively studied. METHODS: Patients with subarachnoid hemorrhage were prospectively followed in an observational database. Demographic information including ethnicity was collected from medical records and self-reported by patients or their family. Significant in-hospital events including do-not-resuscitate orders, comfort measures only orders (CMO; care withheld or withdrawn), and mortality were recorded prospectively. RESULTS: 1255 patients were included in our analysis: 650 (52 %) were White, 387 (31 %) Hispanic, and 218 (17 %) Black. Mortality was similar between the groups. CMO was more commonly observed in Whites (14 %) compared to either Blacks (10 %) or Hispanics (9 %) (p = 0.04). In a multivariate analysis controlling for age and Hunt-Hess grade, Hispanics were less likely to have CMO than Whites (OR, 0.6; 95 %CI, 0.4-0.9; p = 0.02). Of the 229 patients who died, 77 % of Whites had CMO compared to 54 % of Blacks and 49 % of Hispanics (p < 0.01). In a multivariate analysis, Blacks (OR, 0.3; 95 %CI, 0.2-0.7; p < 0.01) and Hispanics (OR, 0.3; 95 %CI, 0.2-0.6; p < 0.01) were less likely to die with CMO orders than Whites. CONCLUSION: After subarachnoid hemorrhage, Blacks and Hispanics are less likely to die with CMO orders than Whites. Further research to confirm and investigate the causes of these ethnic differences should be performed.

Brain injury visible on early MRI after subarachnoid hemorrhage might predict neurological impairment and functional outcome.

BACKGROUND: In subarachnoid hemorrhage (SAH), brain injury visible within 48 h of onset may impact on admission neurological disability and 3-month functional outcome. With volumetric MRI, we measured the volume of brain injury visible after SAH, and assessed the association with admission clinical grade and 3-month functional outcome. METHODS: Retrospective cohort study conducted in the Neurocritical Care Division, Columbia University Medical Center, New York, USA. On brain MRI acquired within 48 h of SAH-onset and before aneurysm-securing (n = 27), two blinded readers measured DWI and FLAIR-lesion volumes using semi-automated, computer segmentation software. RESULTS: Compared to post-resuscitation Hunt-Hess grade 1-3 (70 %), high-grade patients (30 %) had higher lesion volumes on DWI (34 ml [IQR: 0-64] vs. 2 ml [IQR: 0.5-7], P = 0.02) and on FLAIR (81 ml [IQR: 24-127] vs. 3 ml [IQR: 0-27], P = 0.02). On DWI, each 10 ml increase in lesion volume was associated with a 101 %-increase in the odds of presenting with 1 grade more in the Hunt-Hess scale (aOR 2.01, 95 % CI 1.10-3.68, P = 0.02), but was not significantly associated with 3-month outcome. On FLAIR, each 10 ml increase in lesion volume was associated with 34 % higher odds of a 1-point increase on the Hunt-Hess scale (aOR 1.34, 95 % CI 1.06-1.68, P = 0.01) and 139 % higher odds of a 1-point increase on the 3-month mRS (aOR 2.39, 95 % CI 1.13-5.07, P = 0.02). CONCLUSION: The volume of brain injury visible on DWI and FLAIR within 48 h after SAH is proportional to neurological impairment on admission. Moreover, FLAIR-imaging implicates chronic brain injury-predating SAH-as potentially relevant cause of poor functional outcome.

Nonconvulsive seizures after subarachnoid hemorrhage: Multimodal detection and outcomes.

OBJECTIVE: Seizures have been implicated as a cause of secondary brain injury, but the systemic and cerebral physiologic effects of seizures after acute brain injury are poorly understood. METHODS: We analyzed intracortical electroencephalographic (EEG) and multimodality physiological recordings in 48 comatose subarachnoid hemorrhage patients to better characterize the physiological response to seizures after acute brain injury. RESULTS: Intracortical seizures were seen in 38% of patients, and 8% had surface seizures. Intracortical seizures were accompanied by elevated heart rate (p = 0.001), blood pressure (p < 0.001), and respiratory rate (p < 0.001). There were trends for rising cerebral perfusion pressure (p = 0.03) and intracranial pressure (p = 0.06) seen after seizure onset. Intracortical seizure-associated increases in global brain metabolism, partial brain tissue oxygenation, and regional cerebral blood flow (rCBF) did not reach significance, but a trend for a pronounced delayed rCBF rise was seen for surface seizures (p = 0.08). Functional outcome was very poor for patients with severe background attenuation without seizures and best for those without severe attenuation or seizures (77% vs 0% dead or severely disabled, respectively). Outcome was intermediate for those with seizures independent of the background EEG and worse for those with intracortical only seizures when compared to those with intracortical and scalp seizures (50% and 25% death or severe disability, respectively). INTERPRETATION: We replicated in humans complex physiologic processes associated with seizures after acute brain injury previously described in laboratory experiments and illustrated differences such as the delayed increase in rCBF. These real world physiologic observations may permit more successful translation of laboratory research to the bedside.

Hyperoxia may be related to delayed cerebral ischemia and poor outcome after subarachnoid haemorrhage.

OBJECTIVE: To determine the association between exposure to hyperoxia and the risk of delayed cerebral ischaemia (DCI) after subarachnoid haemorrhage (SAH). METHODS: We analysed data from a single centre, prospective, observational cohort database. Patient inclusion criteria were age ≥18 years, aneurysmal SAH, endotracheal intubation with mechanical ventilation, and arterial partial pressure of oxygen (PaO2) measurements. Hyperoxia was defined as the highest quartile of an area under the curve of PaO2, until the development of DCI (PaO2≥173 mm Hg). Poor outcome was defined as modified Rankin Scale 4-6 at 3 months after SAH. RESULTS: Of 252 patients, there were no differences in baseline characteristics between the hyperoxia and control group. Ninety-seven (38.5%) patients developed DCI. The hyperoxia group had a higher incidence of DCI (p<0.001) and poor outcome (p=0.087). After adjusting for modified Fisher scale, rebleeding, global cerebral oedema, intracranial pressure crisis, pneumonia and sepsis, hyperoxia was independently associated with DCI (OR, 3.16; 95% CI 1.69 to 5.92; p<0.001). After adjusting for age, Hunt-Hess grade, aneurysm size, Acute Physiology and Chronic Health Evaluation II score, rebleeding, pneumonia and sepsis, hyperoxia was independently associated with poor outcome (OR, 2.30; 95% CI 1.03 to 5.12; p=0.042). CONCLUSIONS: In SAH patients, exposure to hyperoxia was associated with DCI. Our findings suggest that exposure to excess oxygen after SAH may represent a modifiable factor for morbidity and mortality in this population.

Impact of premorbid hypertension on haemorrhage severity and aneurysm rebleeding risk after subarachnoid haemorrhage.

OBJECTIVE: Arterial hypertension (HTN) is a risk factor for subarachnoid haemorrhage (SAH). We aimed to assess the impact of premorbid HTN on the severity of initial bleeding and the risk of aneurysm rebleeding after SAH. DESIGN: Retrospective analysis of a prospective cohort study of all SAH patients admitted to Columbia University Medical Center between 1996 and 2012. RESULTS: We enrolled 1312 consecutive patients with SAH; 643 (49%) had premorbid HTN. Patients with premorbid HTN presented more frequently as Hunt-Hess Grade IV or V (36% vs 25%, p<0.001) and World Federation of Neurosurgical Societies (WFNS) Grade 4 or 5 (42.6% vs 28.2%, p<0.001), with larger amounts of subarachnoid (Hijdra Sum Score 17 vs 14, p<0.001) and intraventricular blood (median IVH sum score 2 vs 1, p<0.001), and more often with intracerebral haemorrhage (20% vs 13%, p=0.002). In multivariate analysis, patients with premorbid HTN had a higher risk of in-hospital aneurysm rebleeding (11.8% vs 5.5%, adjusted OR 1.67, 95% CI 1.02 to 2.74, p=0.04) after adjusting for age, admission, Hunt-Hess grade, size and site of the ruptured aneurysm. CONCLUSIONS: Premorbid HTN is associated with increased severity of the initial bleeding event and represents a significant risk factor for aneurysm rebleeding. Given that aneurysm rebleeding is a potentially fatal-but preventable-complication, these findings are of clinical relevance.

Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study.

INTRODUCTION: Seizures refractory to third-line therapy are also labeled super-refractory status epilepticus (SRSE). These seizures are extremely difficult to control and associated with poor outcome. We aimed to characterize efficacy and side-effects of continuous infusions of pentobarbital (cIV-PTB) treating SRSE. METHODS: We retrospectively reviewed continuous electroencephalography (cEEG) reports for all adults with RSE treated with cIV-PTB between May 1997 and April 2010 at our institution. Patients with post-anoxic SE and those receiving cIV-PTB for reasons other than RSE were excluded. We collected baseline information, cEEG findings, side-effects and functional outcome at discharge and one year. RESULTS: Thirty one SRSE patients treated with cIV-PTB for RSE were identified. Mean age was 48 years old (interquartile range (IQR) 28,63), 26% (N = 8) had a history of epilepsy. Median SE duration was 6.5 days (IQR 4,11) and the mean duration of cIV-PTB was 6 days (IQR 3,14). 74% (N = 23) presented with convulsive SE. Underlying etiology was acute symptomatic seizures in 52% (N = 16; 12/16 with encephalitis), remote 30% (N = 10), and unknown 16% (N = 5). cIV-PTB controlled seizures in 90% (N = 28) of patients but seizures recurred in 48% (N = 15) while weaning cIV-PTB, despite the fact that suppression-burst was attained in 90% (N = 28) of patients and persisted >72 hours in 56% (N = 17). Weaning was successful after adding phenobarbital in 80% (12/15 of the patients with withdrawal seizures). Complications during or after cIV-PTB included pneumonia (32%, N = 10), hypotension requiring pressors (29%, N = 9), urinary tract infection (13%, N = 4), and one patient each with propylene glycol toxicity and cardiac arrest. One-third (35%, N = 11) had no identified new complication after starting cIV-PTB. At one year after discharge, 74% (N = 23) were dead or in a state of unresponsive wakefulness, 16% (N = 5) severely disabled, and 10% (N = 3) had no or minimal disability. Death or unresponsive wakefulness was associated with catastrophic etiology (p = 0.03), but none of the other collected variables. CONCLUSIONS: cIV-PTB effectively aborts SRSE and complications are infrequent; outcome in this highly refractory cohort of patients with devastating underlying etiologies remains poor. Phenobarbital may be particularly helpful when weaning cIV-PTB.

Multimodality monitoring: informatics, integration data display and analysis.

The goal of multimodality neuromonitoring is to provide continuous, real-time assessment of brain physiology to prevent, detect, and attenuate secondary brain injury. Clinical informatics deals with biomedical data, information, and knowledge including their acquisition, storage, retrieval, and optimal use for clinical decision-making. An electronic literature search was conducted for English language articles describing the use of informatics in the intensive care unit setting from January 1990 to August 2013. A total of 64 studies were included in this review. Clinical informatics infrastructure should be adopted that enables a wide range of linear and nonlinear analytical methods be applied to patient data. Specific time epochs of clinical interest should be reviewable. Analysis strategies of monitor alarms may help address alarm fatigue. Ergonomic data display that present results from analyses with clinical information in a sensible uncomplicated manner improve clinical decision-making. Collecting and archiving the highest resolution physiologic and phenotypic data in a comprehensive open format data warehouse is a crucial first step toward information management and two-way translational research for multimodality monitoring. The infrastructure required is largely the same as that needed for telemedicine intensive care applications, which under the right circumstances improves care quality while reducing cost.

Heart rate variability for preclinical detection of secondary complications after subarachnoid hemorrhage.

BACKGROUND: We sought to determine if monitoring heart rate variability (HRV) would enable preclinical detection of secondary complications after subarachnoid hemorrhage (SAH). METHODS: We studied 236 SAH patients admitted within the first 48 h of bleed onset, discharged after SAH day 5, and had continuous electrocardiogram records available. The diagnosis and date of onset of infections and DCI events were prospectively adjudicated and documented by the clinical team. Continuous ECG was collected at 240 Hz using a high-resolution data acquisition system. The Tompkins-Hamilton algorithm was used to identify R-R intervals excluding ectopic and abnormal beats. Time, frequency, and regularity domain calculations of HRV were generated over the first 48 h of ICU admission and 24 h prior to the onset of each patient's first complication, or SAH day 6 for control patients. Clinical prediction rules to identify infection and DCI events were developed using bootstrap aggregation and cost-sensitive meta-classifiers. RESULTS: The combined infection and DCI model predicted events 24 h prior to clinical onset with high sensitivity (87 %) and moderate specificity (66 %), and was more sensitive than models that predicted either infection or DCI. Models including clinical and HRV variables together substantially improved diagnostic accuracy (AUC 0.83) compared to models with only HRV variables (AUC 0.61). CONCLUSIONS: Changes in HRV after SAH reflect both delayed ischemic and infectious complications. Incorporation of concurrent disease severity measures substantially improves prediction compared to using HRV alone. Further research is needed to refine and prospectively evaluate real-time bedside HRV monitoring after SAH.