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.

Posttraumatic stress and depressive symptoms characterize cardiac arrest survivors' perceived recovery at hospital discharge.

OBJECTIVE: To test the hypothesis that posttraumatic stress and depressive symptoms, not cognitive or functional impairment, are associated with cardiac arrest survivors' negative recovery perceptions at hospital discharge. METHODS: Prospective observational cohort of cardiac arrest patients admitted between 9/2015-5/2017. Survival to discharge with sufficient mental status to complete a psychosocial interview was the main inclusion criterion. Perceived recovery was assessed through the question, "Do you feel that you have made a complete recovery from your arrest?" The following measures were examined as potential correlates of perceived recovery: Repeatable Battery for Assessment of Neuropsychological Status, Modified Lawton Physical Self-Maintenance Scale, Barthel Index, Modified Rankin Scale, Cerebral Performance Category, Center for Epidemiological Studies-Depression (CES-D), and PTSD Checklist-Specific (PCL-S). Logistic regression evaluated associations between perceived recovery and potential correlates of recovery. RESULTS: 64/354 patients (58% men, 48% white, mean age 52 ±â€¯17) were included. 67% (n = 43) had a negative recovery perception. There were no differences among patients' cognitive and functional domains. In individual models, patients with higher PCL-S and CES-D scores were more likely to have a negative recovery perception after adjusting for age and gender (OR: 1.2, 95% CI [1.1, 1.4], p = 0.003) and (OR: 1.1, 95% CI [1.0, 1.1], p = 0.05). CONCLUSIONS: Within one month after a cardiac arrest event, survivors' negative recovery perceptions are associated with psychological distress.

Prognostic Value of the Neurological Examination in Cardiac Arrest Patients After Therapeutic Hypothermia.

OBJECTIVES: Current prognostication guidelines for cardiac arrest (CA) survivors predate the use of therapeutic hypothermia (TH). The prognostic value and ideal timing of the neurological examination remain unknown in the setting of TH. DESIGN: Patients (N = 291) admitted between 2007 and 2015 to Columbia University intensive care units for TH following CA had neurological examinations performed on days 1, 3, 5, and 7 postarrest. Absent pupillary light response (PLR), absent corneal reflexes (CRs), and Glasgow coma scores motor (GCS-M) no better than extension were considered poor examinations. Poor outcome was recorded as cerebral performance category score ≥3 at discharge and 1 year. Predictive values of examination maneuvers were calculated for each time point. MAIN RESULTS: Among the 137 survivors to day 7, sensitivities and negative predictive values were low at all time points. The PLR had false positive rates (FPRs) of 0% and positive predictive values (PPV) of 100% from day 3 onward. For the CR and GCS-M, the FPRs decreased from day 3 to 5 (9% vs 3%; 21% vs 9%), while PPVs increased (91% vs 96%; 90% vs 95%). Excluding patients who died due to withdrawal of life-sustaining therapy (WLST) did not significantly affect FPRs or PPVs, nor did assessing outcome at 1 year. CONCLUSIONS: A poor neurological examination remains a strong predictor of poor outcome, both at hospital discharge and at 1 year, independent of WLST. Following TH, the predictive value of the examination is insufficient at day 3 and should be delayed until at least day 5, with some additional benefit beyond day 5.

Intracortical electrophysiological correlates of blood flow after severe SAH: A multimodality monitoring study.

Subarachnoid hemorrhage (SAH) is a devastating form of stroke. Approximately one in four patients develop progressive neurological deterioration and silent infarction referred to as delayed cerebral ischemia (DCI). DCI is a complex, multifactorial secondary brain injury pattern and its pathogenesis is not fully understood. We aimed to study the relationship between cerebral blood flow (CBF) and neuronal activity at both the cortex and in scalp using electroencephalography (EEG) in poor-grade SAH patients undergoing multimodality intracranial neuromonitoring. Twenty patients were included, of whom half had DCI median 4.7 days (interquartile range (IQR): 4.0-5.6) from SAH bleed. The rate of decline in regional cerebral blood flow (rCBF) was significant in both those with and without DCI and occurred between days 4 and 7 post-SAH. The scalp EEG alpha-delta ratio declined early in those with DCI. In the group without DCI, CBF and cortical EEG alpha-delta ratio were correlated (r = 0.53; p < 0.01) and in the group without DCI, inverse neurovascular coupling was observed at CPP < 80 mmHg. We found preliminary evidence that as patients enter the period of highest risk for the development of DCI, the absence of neurovascular coupling may act as a possible pathomechanism in the development of ischemia following SAH.

Electroencephalographic Periodic Discharges and Frequency-Dependent Brain Tissue Hypoxia in Acute Brain Injury.

Importance: Periodic discharges (PDs) that do not meet seizure criteria, also termed the ictal interictal continuum, are pervasive on electroencephalographic (EEG) recordings after acute brain injury. However, their association with brain homeostasis and the need for clinical intervention remain unknown. Objective: To determine whether distinct PD patterns can be identified that, similar to electrographic seizures, cause brain tissue hypoxia, a measure of ongoing brain injury. Design, Setting, and Participants: This prospective cohort study included 90 comatose patients with high-grade spontaneous subarachnoid hemorrhage who underwent continuous surface (scalp) EEG (sEEG) recording and multimodality monitoring, including invasive measurements of intracortical (depth) EEG (dEEG), partial pressure of oxygen in interstitial brain tissue (Pbto2), and regional cerebral blood flow (CBF). Patient data were collected from June 1, 2006, to September 1, 2014, at a single tertiary care center. The retrospective analysis was performed from September 1, 2014, to May 1, 2016, with a hypothesis that the effect on brain tissue oxygenation was primarily dependent on the discharge frequency. Main Outcomes and Measures: Electroencephalographic recordings were visually classified based on PD frequency and spatial distribution of discharges. Correlations between mean multimodality monitoring data and change-point analyses were performed to characterize electrophysiological changes by applying bootstrapping. Results: Of the 90 patients included in the study (26 men and 64 women; mean [SD] age, 55 [15] years), 32 (36%) had PDs on sEEG and dEEG recordings and 21 (23%) on dEEG recordings only. Frequencies of PDs ranged from 0.5 to 2.5 Hz. Median Pbto2 was 23 mm Hg without PDs compared with 16 mm Hg at 2.0 Hz and 14 mm Hg at 2.5 Hz (differences were significant for 0 vs 2.5 Hz based on bootstrapping). Change-point analysis confirmed a temporal association of high-frequency PD onset (≥2.0 Hz) and Pbto2 reduction (median normalized Pbto2 decreased by 25% 5-10 minutes after onset). Increased regional CBF of 21.0 mL/100 g/min for 0 Hz, 25.9 mL/100 g/min for 1.0 Hz, 27.5 mL/100 g/min for 1.5 Hz, and 34.7 mL/100 g/min for 2.0 Hz and increased global cerebral perfusion pressure of 91 mm Hg for 0 Hz, 100.5 mm Hg for 0.5 Hz, 95.5 mm Hg for 1.0 Hz, 97.0 mm Hg for 2.0 Hz, 98.0 mm Hg for 2.5 Hz, 95.0 mm Hg for 2.5 Hz, and 67.8 mm Hg for 3.0 Hz were seen for higher PD frequencies. Conclusions and Relevance: These data give some support to consider redefining the continuum between seizures and PDs, suggesting that additional damage after acute brain injury may be reflected by frequency changes in electrocerebral recordings. Similar to seizures, cerebral blood flow increases in patients with PDs to compensate for the increased metabolic demand but higher-frequency PDs (>2 per second) may be inadequately compensated without an additional rise in CBF and associated with brain tissue hypoxia, or higher-frequency PDs may reflect inadequacies in brain compensatory mechanisms.

Ultra-early angiographic vasospasm associated with delayed cerebral ischemia and infarction following aneurysmal subarachnoid hemorrhage.

OBJECTIVE The clinical significance of cerebral ultra-early angiographic vasospasm (UEAV), defined as cerebral arterial narrowing within the first 48 hours of aneurysmal subarachnoid hemorrhage (aSAH), remains poorly characterized. The authors sought to determine its frequency, predictors, and impact on functional outcome. METHODS The authors prospectively studied UEAV in a cohort of 1286 consecutively admitted patients with aSAH between August 1996 and June 2013. Admission clinical, radiographic, and acute clinical course information was documented during patient hospitalization. Functional outcome was assessed at 3 months using the modified Rankin Scale. Logistic regression and Cox proportional hazards models were generated to assess predictors of UEAV and its relationship to delayed cerebral ischemia (DCI) and outcome. Multiple imputation methods were used to address data lost to follow-up. RESULTS The cohort incidence rate of UEAV was 4.6%. Multivariable logistic regression analysis revealed that younger age, sentinel bleed, and poor admission clinical grade were significantly associated with UEAV. Patients with UEAV had a 2-fold increased risk of DCI (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.4-3.9, p = 0.002) and cerebral infarction (OR 2.0, 95% CI 1.0-3.9, p = 0.04), after adjusting for known predictors. Excluding patients who experienced sentinel bleeding did not change this effect. Patients with UEAV also had a significantly higher hazard for DCI in a multivariable model. UEAV was not found to be significantly associated with poor functional outcome (OR 0.8, 95% CI 0.4-1.6, p = 0.5). CONCLUSIONS UEAV may be less frequent than has been reported previously. Patients who exhibit UEAV are at higher risk for refractory DCI that results in cerebral infarction. These patients may benefit from earlier monitoring for signs of DCI and more aggressive treatment. Further study is needed to determine the long-term functional significance of UEAV.

Causal Structure of Brain Physiology after Brain Injury from Subarachnoid Hemorrhage.

High frequency physiologic data are routinely generated for intensive care patients. While massive amounts of data make it difficult for clinicians to extract meaningful signals, these data could provide insight into the state of critically ill patients and guide interventions. We develop uniquely customized computational methods to uncover the causal structure within systemic and brain physiologic measures recorded in a neurological intensive care unit after subarachnoid hemorrhage. While the data have many missing values, poor signal-to-noise ratio, and are composed from a heterogeneous patient population, our advanced imputation and causal inference techniques enable physiologic models to be learned for individuals. Our analyses confirm that complex physiologic relationships including demand and supply of oxygen underlie brain oxygen measurements and that mechanisms for brain swelling early after injury may differ from those that develop in a delayed fashion. These inference methods will enable wider use of ICU data to understand patient physiology.

Predictors of Poor Quality of Life 1 Year After Subarachnoid Hemorrhage.

BACKGROUND: Risk factors for poor quality of life (QOL) after subarachnoid hemorrhage (SAH) remain poorly described. OBJECTIVE: To identify the frequency and predictors of poor QOL 1 year after SAH. METHODS: We studied 1-year QOL in a prospectively collected cohort of 1181 consecutively admitted SAH survivors between July 1996 and May 2013. Patient clinical, radiographic, surgical, and acute clinical course information was recorded. Reduced QOL (overall, physical, and psychosocial) at 1 year was assessed with the Sickness Impact Profile and defined as 2 SD below population-based normative Sickness Impact Profile values. Logistic regression leveraging multiple imputation to handle missing data was used to evaluate reduced QOL. RESULTS: Poor overall QOL was observed in 35% of patients. Multivariable analysis revealed that nonwhite ethnicity, high school education or less, history of depression, poor clinical grade (Hunt-Hess Grade ≥3), and delayed infarction were predictors of poor overall and psychosocial QOL. Poor physical QOL was additionally associated with older age, hydrocephalus, pneumonia, and sepsis. At 1 year, patients with poor QOL had increased difficulty concentrating, cognitive dysfunction, depression, and reduced activities of daily living. More than 91% of patients with poor QOL failed to fully return to work. These patients frequently received physical rehabilitation, but few received cognitive rehabilitation or emotional-behavioral support. CONCLUSION: Reduced QOL affects as many as one-third of SAH survivors 1 year after SAH. Delayed infarction is the most important in-hospital modifiable factor that affects QOL. Increased attention to cognitive and emotional difficulties after hospital discharge may help patients achieve greater QOL.

Loss of Consciousness at Onset of Subarachnoid Hemorrhage as an Important Marker of Early Brain Injury.

IMPORTANCE: Loss of consciousness (LOC) is a common presenting symptom of subarachnoid hemorrhage (SAH) that is presumed to result from transient intracranial circulatory arrest. OBJECTIVE: To clarify the association between LOC at onset of SAH, complications while in the hospital, and long-term outcome after SAH. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was conducted of 1460 consecutively treated patients with spontaneous SAH who were part of a prospective observational cohort study at a large urban academic medical center (the Columbia University SAH Outcomes Project or SHOP). Patients were enrolled between August 6, 1996, and July 23, 2012. Analysis was conducted from December 1, 2013, to February 28, 2015. EXPOSURES: Loss of consciousness at onset was identified by structured interview of the patient and first responders. Patients (80.5%) were observed for up to 1 year to assess functional recovery. MAIN OUTCOMES AND MEASURES: Modified Rankin scale scores were assigned based on telephone or in-person interviews of the patient, family members, or caregivers. Complications while in the hospital were predefined and adjudicated by the study team. RESULTS: Five hundred ninety patients (40.4%) reported LOC at onset of SAH. Loss of consciousness was associated with poor clinical grade, more subarachnoid and intraventricular blood seen on admission computed tomographic scan, and a higher frequency of global cerebral edema (P < .001). Loss of consciousness was also associated with more prehospital tonic-clonic activity (22.7% vs 4.2%; P < .001) and cardiopulmonary arrest (9.7% vs 0.5%, P < .001) vs patients who did not experience LOC. In multivariable analysis, death or severe disability at 12 months was independently associated with LOC after adjusting for established risk factors for poor outcome, including poor admission clinical grade (adjusted odds ratio, 1.94; 95% CI, 1.38-2.72; P < .001). There was no association between LOC at onset and delayed cerebral ischemia or aneurysm rebleeding. CONCLUSIONS AND RELEVANCE: Loss of consciousness at symptom onset is an important manifestation of early brain injury after SAH and a predictor of death or poor functional outcome at 12 months.

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.

Prolonged elevated heart rate is a risk factor for adverse cardiac events and poor outcome after subarachnoid hemorrhage.

INTRODUCTION: Sympathetic nervous system hyperactivity is common after subarachnoid hemorrhage (SAH). We sought to determine whether uncontrolled prolonged heart rate elevation is a risk factor for adverse cardiopulmonary events and poor outcome after SAH. METHODS: We prospectively studied 447 SAH patients between March 2006 and April 2012. Prior studies define prolonged elevated heart rate (PEHR) as heart rate >95 beats/min for >12 h. Major adverse cardiopulmonary events were documented according to the predefined criteria. Global outcome at 3 months was assessed with the modified Rankin Scale (mRS). RESULTS: 175 (39 %) patients experienced PEHR. Nonwhite race/ethnicity, admission Hunt-Hess grade ≥4, elevated APACHE-2 physiological subscore, and modified Fisher score were significant admission predictors of PEHR, whereas documented pre-hospital beta-blocker use was protective. After controlling for admission Hunt-Hess grade, Cox regression using time-lagged covariates revealed that PEHR onset in the previous 48 h was associated with an increased hazard for delayed cerebral ischemia, myocardial injury, and pulmonary edema. PEHR was associated with 3-month poor outcome (mRS 4-6) after controlling for known predictors. CONCLUSIONS: PEHR is associated with major adverse cardiopulmonary events and poor outcome after SAH. Further study is warranted to determine if early sympatholytic therapy targeted at sustained heart rate control can improve outcome after SAH.