Perioperative stroke.

Ischaemic or haemorrhagic perioperative stroke (that is, stroke occurring during or within 30 days following surgery) can be a devastating complication following surgery. Incidence is reported in the 0.1-0.7% range in adults undergoing non-cardiac and non-neurological surgery, in the 1-5% range in patients undergoing cardiac surgery and in the 1-10% range following neurological surgery. However, higher rates have been reported when patients are actively assessed and in high-risk populations. Prognosis is significantly worse than stroke occurring in the community, with double the 30-day mortality, greater disability and diminished quality of life among survivors. Considering the annual volume of surgeries performed worldwide, perioperative stroke represents a substantial burden. Despite notable differences in aetiology, patient populations and clinical settings, existing clinical recommendations for perioperative stroke are extrapolated mainly from stroke in the community. Perioperative in-hospital stroke is unique with respect to the stroke occurring in other settings, and it is essential to apply evidence from other settings with caution and to identify existing knowledge gaps in order to effectively guide patient care and future research.

Microvascular reperfusion during endovascular therapy: the balance of supply and demand.

BACKGROUND: Endovascular therapy (EVT) has revolutionized the treatment of acute stroke, but large vessel recanalization does not always result in tissue-level reperfusion. Cerebral blood flow (CBF) is not routinely monitored during EVT. We aimed to leverage diffuse correlation spectroscopy (DCS), a novel transcranial optical imaging technique, to assess the relationship between microvascular CBF and post-EVT outcomes. METHODS: Frontal lobe CBF was monitored by DCS in 40 patients undergoing EVT. Baseline CBF deficit was calculated as the percentage of CBF impairment on pre-EVT CT perfusion. Microvascular reperfusion was calculated as the percentage increase in DCS-derived CBF that occurred with recanalization. The adequacy of reperfusion was defined by persistent CBF deficit, calculated as: baseline CBF deficit - microvascular reperfusion. A good functional outcome was defined as 90-day modified Rankin Scale score ≤2. RESULTS: Thirty-six of 40 patients achieved successful recanalization, in whom microvascular reperfusion in itself was not associated with infarct volume or functional outcome. However, patients with good functional outcomes had a smaller persistent CBF deficit (median 1% (IQR -11%-16%)) than patients with poor outcomes (median 28% (IQR 2-50%)) (p=0.02). Smaller persistent CBF deficit was also associated with smaller infarct volume (p=0.004). Multivariate models confirmed that persistent CBF deficit was independently associated with infarct volume and functional outcome. CONCLUSIONS: CBF augmentation alone does not predict post-EVT outcomes, but when microvascular reperfusion closely matches the baseline CBF deficit, patients experience favorable clinical and radiographic outcomes. By recognizing inadequate reperfusion, bedside CBF monitoring may provide opportunities to personalize post-EVT care aimed at CBF optimization.

Preoperative cognition predicts clinical stroke/TIA and mortality after surgical aortic valve replacement in older adults.

Stroke and death remain risks of surgical aortic valve replacement (SAVR). Preoperative cognitive screeners repeatedly show that reduced scores predict postoperative outcome, but less is known about comprehensive neuropsychological measures predicting risk. This study had two aims: 1) investigate whether preoperative cognitive measures predicted postoperative clinical stroke/transient ischemic attack (TIA) and mortality in older adults undergoing SAVR, and 2) identify the best predictors within a comprehensive cognitive protocol. A total of 165 participants aged 65 + with moderate-to-severe aortic stenosis completed a comprehensive cognitive test battery preoperatively. Postoperative stroke evaluations were conducted by trained stroke neurologists preoperatively and postoperatively, and mortality outcomes were obtained by report and records. Logistic regressions were conducted to evaluate preoperative cognitive predictors of clinical stroke/TIA within 1 week of surgery and mortality within 1 year of surgery. Multivariate models showed measures of delayed verbal memory recall (OR = 0.86; 95% CI 0.74-0.99) and visuospatial skills (OR = 0.95; 95% CI 0.90-1.01) predicted clinical stroke/TIA within 1 week of surgery, R2 = .41, p < .001, ƒ2 = .69. Measures of naming ability (OR = 0.88; 95% CI 0.80-0.96), verbal memory recall (OR = 1.23; 95% CI 0.99-1.51), visual memory recall (OR = 0.90; 95% CI 0.80-1.00), medical comorbidities (OR = 1.71; 95% CI 1.22-2.65), and sex (OR = 2.39; 95% CI 0.90-7.04) were significant predictors of death within 1 year of surgery, R2 = .68, p < .001, ƒ2 = 2.12. Preoperative cognitive measures reflecting temporal and parietal lobe functions predicted postoperative clinical stroke/TIA within 1 week of SAVR and mortality within 1 year of SAVR. As such, cognitive measures may offer objective and timely indicators of preoperative health, specifically vulnerabilities in cerebral hypoperfusion, which may inform intervention and/or intensive postoperative monitoring and follow-up after SAVR.

The impact of perioperative stroke and delirium on outcomes after surgical aortic valve replacement.

OBJECTIVE: The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days. METHODS: Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life. RESULTS: By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score >2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01). CONCLUSIONS: Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

Delays in the Identification and Assessment of in-Hospital Stroke Patients.

OBJECTIVES: In-hospital stroke is associated with poor outcomes. Reasons for delays, use of interventions, and presence of large vessel occlusion are not well characterized. MATERIALS AND METHODS: A retrospective single center cohort of 97 patients with in-hospital stroke was analyzed to identify factors associated with delays from last known normal to symptom identification and to stroke team alerting. Stroke interventions and presence of large vessel occlusion were also assessed. RESULTS: Strokes were predominantly on surgery services (70%), ischemic (82%), and severe (median NIHSS 16; interquartile range [IQR] 6-24). There were long delays from last known normal to symptom identification (median 5.1 hours, IQR 1.0-19.7 hours), symptom identification to stroke team alerting (median 2.1 hours, IQR 0.5-9.9 hours), and total time from last known normal to alerting (median 11.4 [IQR 2.7-34.2] hours). In univariable analysis, being on a surgical service, in an ICU, intubated, and higher NIHSS were associated with delays. In multivariable analysis only intubation was independently associated with time from last known normal to symptom identification (coefficient 20 hours, IQR 0.2 - 39.8, p=0.047). Interventions were given to 17/80 (21%) ischemic stroke patients; 3 (4%) received IV tPA and 14 (18%) underwent thrombectomy. Vascular imaging occurred in 57/80 (71%) ischemic stroke patients and 21/57 (37%) had large vessel occlusion. CONCLUSIONS: Hospitalized patients with stroke experience long delays from symptom identification to stroke team alerting. Intubation was strongly associated with delay to symptom identification. Although stroke severity was high and large vessel occlusion common, many patients did not receive acute interventions.

Frequency and Patterns of Brain Infarction in Patients With Embolic Stroke of Undetermined Source: NAVIGATE ESUS Trial.

BACKGROUND AND PURPOSE: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. METHODS: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. RESULTS: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26-115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack (P<0.001), modified Rankin Scale score >0 (P<0.001), and current tobacco use (P=0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. CONCLUSIONS: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.

Perioperative Neurological Evaluation and Management to Lower the Risk of Acute Stroke in Patients Undergoing Noncardiac, Nonneurological Surgery: A Scientific Statement From the American Heart Association/American Stroke Association.

Perioperative stroke is a potentially devastating complication in patients undergoing noncardiac, nonneurological surgery. This scientific statement summarizes established risk factors for perioperative stroke, preoperative and intraoperative strategies to mitigate the risk of stroke, suggestions for postoperative assessments, and treatment approaches for minimizing permanent neurological dysfunction in patients who experience a perioperative stroke. The first section focuses on preoperative optimization, including the role of preoperative carotid revascularization in patients with high-grade carotid stenosis and delaying surgery in patients with recent strokes. The second section reviews intraoperative strategies to reduce the risk of stroke, focusing on blood pressure control, perioperative goal-directed therapy, blood transfusion, and anesthetic technique. Finally, this statement presents strategies for the evaluation and treatment of patients with suspected postoperative strokes and, in particular, highlights the value of rapid recognition of strokes and the early use of intravenous thrombolysis and mechanical embolectomy in appropriate patients.

D-dimer and Body CT to Identify Occult Malignancy in Acute Ischemic Stroke.

BACKGROUND AND AIM: Patients with acute ischemic stroke associated with cancer have D-dimer elevations greater than those with acute ischemic stroke or cancer alone. While D-dimer has been proposed as a screening tool to identify such patients, its use in clinical practice to identify malignancy and to inform the use of CT scanning has not been well characterized. METHODS: We conducted a retrospective cohort study of patients with acute ischemic stroke to evaluate how D-dimer levels and CT chest, abdomen, and pelvis scanning were used in practice to screen for occult malignancy. Patients were excluded if they had known active cancer and or received tPA. RESULTS: Of 480 patients, 254 (53%) had D-dimer measured, 49 (10%) underwent CT screening for cancer, and 11 (2%) had findings concerning for malignancy. There was no difference in D-dimer level between patients who underwent CT evaluation for cancer and those who did not (median 1.01 vs 0.85 p = 0.19). Patients with CT concerning for cancer had higher D-dimer levels than those with a negative CT (median 2.52 vs 0.74 p = 0.01). D-dimer demonstrated moderate discrimination with a c-statistic of 0.77. Selecting a cut point of >1.2 ug/mL (60th percentile of our cohort and 2.4-times the upper limit of normal for our institution's D-dimer assay) provided a sensitivity of 85% and specificity of 65%, a positive likelihood ratio of 2.32, and an odds ratio of 9.6 (95% confidence interval 2.1-44.1, p = 0.004) for having a CT scan concerning for malignancy. CONCLUSIONS: Elevated D-dimer levels are suggestive of occult malignancy in acute ischemic stroke patients and should inform selective use of CT to screen for cancer.

Considerations for Reduction of Risk of Perioperative Stroke in Adult Patients Undergoing Cardiac and Thoracic Aortic Operations: A Scientific Statement From the American Heart Association.

Perioperative stroke is one of the most severe and feared complications of cardiac surgery. Based on the timing of onset and detection, perioperative stroke can be classified as intraoperative or postoperative. The pathogenesis of perioperative stroke is multifactorial, which makes prediction and prevention challenging. However, information on its incidence, mechanisms, diagnosis, and treatment can be helpful in minimizing the perioperative neurological risk for individual patients. We herein provide suggestions on preoperative, intraoperative, and postoperative strategies aimed at reducing the risk of perioperative stroke and at improving the outcomes of patients who experience a perioperative stroke.

Impact of Aortic Atherosclerosis Burden on Outcomes of Surgical Aortic Valve Replacement.

BACKGROUND: Epiaortic ultrasound detects and localizes ascending aortic atherosclerosis. In this analysis we investigated the association between epiaortic ultrasound-based atheroma grade during surgical aortic valve replacement (SAVR) and perioperative adverse outcomes. METHODS: SAVR patients in a randomized trial of 2 embolic protection devices underwent a protocol-defined 5-view epiaortic ultrasound read at a core laboratory. Aortic atherosclerosis was quantified with the Katz atheroma grade, and patients were categorized as mild (grade I-II) or moderate/severe (grade III-V). Multivariable logistic regression was used to estimate associations between atheroma grade and adverse outcomes, including death, clinically apparent stroke, cerebral infarction on diffusion-weighted magnetic resonance imaging, delirium, and acute kidney injury (AKI) by 7 and 30 days. RESULTS: Precannulation epiaortic ultrasound data were available for 326 of 383 randomized patients (85.1%). Of these, 106 (32.5%) had moderate/severe Katz atheroma grade at any segment of the ascending aorta. Although differences in the composite of death, stroke, or cerebral infarction on diffusion-weighted magnetic resonance imaging by 7 days were not statistically significant, moderate/severe atheroma grade was associated with a greater risk of AKI by 7 days (adjusted odds ratio, 2.63; 95% confidence interval, 1.24-5.58; P = .01). At 30 days, patients with moderate/severe atheroma grade had a greater risk of death, stroke, or AKI (adjusted odds ratio, 1.97; 95% confidence interval, 1.04-3.71; P = .04). CONCLUSIONS: Moderate/severe aortic atherosclerosis was associated with an increased risk of adverse events after SAVR. Epiaortic ultrasound may serve as a useful adjunct for identifying patients who may benefit from strategies to reduce atheroembolic complications during SAVR.

Effect of Cerebral Embolic Protection Devices on CNS Infarction in Surgical Aortic Valve Replacement: A Randomized Clinical Trial.

Importance: Stroke is a major complication of surgical aortic valve replacement (SAVR). Objective: To determine the efficacy and adverse effects of cerebral embolic protection devices in reducing ischemic central nervous system (CNS) injury during SAVR. Design, Setting, and Participants: A randomized clinical trial of patients with calcific aortic stenosis undergoing SAVR at 18 North American centers between March 2015 and July 2016. The end of follow-up was December 2016. Interventions: Use of 1 of 2 cerebral embolic protection devices (n = 118 for suction-based extraction and n = 133 for intra-aortic filtration device) vs a standard aortic cannula (control; n = 132) at the time of SAVR. Main Outcomes and Measures: The primary end point was freedom from clinical or radiographic CNS infarction at 7 days (± 3 days) after the procedure. Secondary end points included a composite of mortality, clinical ischemic stroke, and acute kidney injury within 30 days after surgery; delirium; mortality; serious adverse events; and neurocognition. Results: Among 383 randomized patients (mean age, 73.9 years; 38.4% women; 368 [96.1%] completed the trial), the rate of freedom from CNS infarction at 7 days was 32.0% with suction-based extraction vs 33.3% with control (between-group difference, -1.3%; 95% CI, -13.8% to 11.2%) and 25.6% with intra-aortic filtration vs 32.4% with control (between-group difference, -6.9%; 95% CI, -17.9% to 4.2%). The 30-day composite end point was not significantly different between suction-based extraction and control (21.4% vs 24.2%, respectively; between-group difference, -2.8% [95% CI, -13.5% to 7.9%]) nor between intra-aortic filtration and control (33.3% vs 23.7%; between-group difference, 9.7% [95% CI, -1.2% to 20.5%]). There were no significant differences in mortality (3.4% for suction-based extraction vs 1.7% for control; and 2.3% for intra-aortic filtration vs 1.5% for control) or clinical stroke (5.1% for suction-based extraction vs 5.8% for control; and 8.3% for intra-aortic filtration vs 6.1% for control). Delirium at postoperative day 7 was 6.3% for suction-based extraction vs 15.3% for control (between-group difference, -9.1%; 95% CI, -17.1% to -1.0%) and 8.1% for intra-aortic filtration vs 15.6% for control (between-group difference, -7.4%; 95% CI, -15.5% to 0.6%). Mortality and overall serious adverse events at 90 days were not significantly different across groups. Patients in the intra-aortic filtration group vs patients in the control group experienced significantly more acute kidney injury events (14 vs 4, respectively; P = .02) and cardiac arrhythmias (57 vs 30; P = .004). Conclusions and Relevance: Among patients undergoing SAVR, cerebral embolic protection devices compared with a standard aortic cannula did not significantly reduce the risk of CNS infarction at 7 days. Potential benefits for reduction in delirium, cognition, and symptomatic stroke merit larger trials with longer follow-up. Trial Registration: clinicaltrials.gov Identifier: NCT02389894.

What Makes New Ischemic Lesions Symptomatic after Aortic Valve Replacement?

BACKGROUND: Acute cerebral infarctions on diffusion-weighted magnetic resonance imaging (MRI) are common after cardiothoracic surgery. However, most are asymptomatic and we aimed to identify features associated with clinical stroke symptoms. METHODS: Patients over 65 years of age undergoing surgical aortic valve replacement (AVR) for calcific stenosis were prospectively recruited (N = 196). All patients underwent neurological evaluation preoperatively and on postoperative days 1, 3, and 7, and MRI on planned postoperative day 5. Among those with new postoperative DWI lesions, we performed univariate and multivariable analyses to identify clinical, demographic, surgical, and imaging factors associated with clinical stroke symptoms. RESULTS: Of the 129 patients who completed a postsurgical MRI, 79 (61%) had DWI lesions and 17 (21.5%) of these had new stroke symptoms concordant with the infarct distribution. In an exploratory multivariable analysis, focal neurological symptoms were associated with increased age, a longer bypass duration, and a larger pre-existing lesion burden on fluid-attenuated inversion recovery. Limiting the analysis to the 61 patients with analyzable volume and location data, logistic regression failed to identify any location-related determinant of symptomatic lesions. CONCLUSIONS: New DWI lesions are common after AVR, but most are asymptomatic. Patients are more likely to have symptoms with longer bypass durations, increasing age, and larger pre-existing lesion burdens.

Pathogenesis and Risk Factors for Cerebral Infarct After Surgical Aortic Valve Replacement.

BACKGROUND AND PURPOSE: Stroke is a potentially devastating complication of cardiac surgery. Identifying predictors of radiographic infarct may lead to improved stroke prevention for surgical patients. METHODS: We reviewed 129 postoperative brain magnetic resonance imagings from a prospective study of patients undergoing surgical aortic valve replacement. Acute infarcts were classified as watershed or embolic using prespecified criteria. RESULTS: Acute infarct on magnetic resonance imaging was seen in 79 of 129 patients (61%), and interrater reliability for stroke pathogenesis was high (κ=0.93). Embolic infarcts only were identified in 60 patients (46%), watershed only in 2 (2%), and both in 17 (13%). In multivariable logistic regression, embolic infarct was associated with aortic arch atheroma (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.0-12.0; P=0.055), old subcortical infarcts (OR, 5.5; 95% CI, 1.1-26.6; P=0.04), no history of percutaneous transluminal coronary angioplasty or coronary artery bypass graft (OR, 4.0; 95% CI, 1.2-13.7; P=0.03), and higher aortic valve gradient (OR, 1.3 per 5 mm Hg; 95% CI, 1.09-1.6; P=0.004). Watershed infarct was associated with internal carotid artery stenosis ≥70% (OR, 11.7; 95% CI, 1.8-76.8; P=0.01) and increased left ventricular ejection fraction (OR, 1.6 per 5% increase; 95% CI, 1.08-2.4; P=0.02). CONCLUSIONS: The principal mechanism of acute cerebral infarction after aortic valve replacement is embolism. There are distinct factors associated with watershed and embolic infarct, some of which may be modifiable.

Stroke after aortic valve surgery: results from a prospective cohort.

BACKGROUND: The incidence and impact of clinical stroke and silent radiographic cerebral infarction complicating open surgical aortic valve replacement (AVR) are poorly characterized. METHODS AND RESULTS: We performed a prospective cohort study of subjects ≥65 years of age who were undergoing AVR for calcific aortic stenosis. Subjects were evaluated by neurologists preoperatively and postoperatively and underwent postoperative magnetic resonance imaging. Over a 4-year period, 196 subjects were enrolled at 2 sites (mean age, 75.8±6.2 years; 36% women; 6% nonwhite). Clinical strokes were detected in 17%, transient ischemic attack in 2%, and in-hospital mortality was 5%. The frequency of stroke in the Society for Thoracic Surgery database in this cohort was 7%. Most strokes were mild; the median National Institutes of Health Stroke Scale was 3 (interquartile range, 1-9). Clinical stroke was associated with increased length of stay (median, 12 versus 10 days; P=0.02). Moderate or severe stroke (National Institutes of Health Stroke Scale ≥10) occurred in 8 (4%) and was strongly associated with in-hospital mortality (38% versus 4%; P=0.005). Of the 109 stroke-free subjects with postoperative magnetic resonance imaging, silent infarct was identified in 59 (54%). Silent infarct was not associated with in-hospital mortality or increased length of stay. CONCLUSIONS: Clinical stroke after AVR was more common than reported previously, more than double for this same cohort in the Society for Thoracic Surgery database, and silent cerebral infarctions were detected in more than half of the patients undergoing AVR. Clinical stroke complicating AVR is associated with increased length of stay and mortality.

Summary of evidence-based guideline: periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease: report of the Guideline Development Subcommittee of the American Academy of Neurology.

OBJECTIVE: To assess evidence regarding periprocedural management of antithrombotic drugs in patients with ischemic cerebrovascular disease. The complete guideline on which this summary is based is available as an online data supplement to this article. METHODS: Systematic literature review with practice recommendations. RESULTS AND RECOMMENDATIONS: Clinicians managing antithrombotic medications periprocedurally must weigh bleeding risks from drug continuation against thromboembolic risks from discontinuation. Stroke patients undergoing dental procedures should routinely continue aspirin (Level A). Stroke patients undergoing invasive ocular anesthesia, cataract surgery, dermatologic procedures, transrectal ultrasound-guided prostate biopsy, spinal/epidural procedures, and carpal tunnel surgery should probably continue aspirin (Level B). Some stroke patients undergoing vitreoretinal surgery, EMG, transbronchial lung biopsy, colonoscopic polypectomy, upper endoscopy and biopsy/sphincterotomy, and abdominal ultrasound-guided biopsies should possibly continue aspirin (Level C). Stroke patients requiring warfarin should routinely continue it when undergoing dental procedures (Level A) and probably continue it for dermatologic procedures (Level B). Some patients undergoing EMG, prostate procedures, inguinal herniorrhaphy, and endothermal ablation of the great saphenous vein should possibly continue warfarin (Level C). Whereas neurologists should counsel that warfarin probably does not increase clinically important bleeding with ocular anesthesia (Level B), other ophthalmologic studies lack the statistical precision to make recommendations (Level U). Neurologists should counsel that warfarin might increase bleeding with colonoscopic polypectomy (Level C). There is insufficient evidence to support or refute periprocedural heparin bridging therapy to reduce thromboembolic events in chronically anticoagulated patients (Level U). Neurologists should counsel that bridging therapy is probably associated with increased bleeding risks as compared with warfarin cessation (Level B). The risk difference as compared with continuing warfarin is unknown (Level U).

A pilot study of darbepoetin alfa for prophylactic neuroprotection in aortic surgery.

BACKGROUND: Descending aortic (DA) surgery poses a high risk for spinal and cerebral infarction and routine use of lumbar drains allows for measurement of CSF markers of neurologic injury. Erythropoiesis medications have extensive preclinical data demonstrating neuroprotection. We hypothesized that prophylactic darbepoetin alfa (DARB) given before surgery reduces neurologic injury in patients undergoing DA repair. METHODS AND RESULTS: We performed a prospective adaptive dose-finding trial of prophylactic DARB ( www.clinicaltrials.gov NCT00647998) that terminated prematurely following publication of an erythropoietin stroke study showing possible harm. Enrollment halted before dose adjustments; nine patients each received 1 mg/kg IV DARB immediately before surgery. A prospective cohort of nine untreated patients was subsequently obtained for comparison. The primary outcome of death or neurologic impairment at discharge occurred in 1/9 (11 %) DARB patients and 3/9 (33 %) controls (p = 0.58). There were no statistical differences in changes of CSF biomarkers from baseline to 48 h comparing DARB patients to controls: S100ß, median 214 versus 260 ng/ml (p = 0.69); glial fibrillary acidic protein (GFAP), median 0.022 versus 0.58 ng/ml (p = 0.45). In patients with early perioperative neurologic ischemia, there were greater changes in CSF biomarkers, compared to those without ischemia: S100ß, median 2301 versus 124 ng/ml (p = 0.04); GFAP, median 31.78 versus 0.31 ng/ml (p = 0.34). CONCLUSIONS: There were no significant effects of prophylactic DARB on clinical outcome or CSF markers of neurologic injury in this pilot study, although all point estimates favored treatment. DA repair is a promising model of prophylactic neuroprotection.

Seizures do not increase in-hospital mortality after intracerebral hemorrhage in the nationwide inpatient sample.

BACKGROUND: Seizures are common after intracerebral hemorrhage (ICH) but their impact on outcome is uncertain and prophylactic anti-convulsant use is controversial. We hypothesized that seizures would not increase the risk of in-hospital mortality in a large administrative database. METHODS: The study population included patients in the 2006 Nationwide Inpatient Sample over the age of 18 with a principal diagnosis of ICH (ICD9 = 431). Subjects with a secondary diagnosis of aneurysm, arterio-venous malformation, brain tumor, or traumatic brain injury were excluded. Seizures were defined by ICD9 codes (345.0x-345.5x, 345.7x-345.9x, 780.39). Logistic regression was used to quantify the relationship between seizures and in-hospital mortality. Pre-specified subgroups included age strata, length of stay, and invasive procedures. RESULTS: 13,033 subjects met all eligibility criteria, of which 1,430 (11.0 %) had a secondary diagnosis of seizure. Subjects with seizure were younger (64 vs. 70 years, p < 0.001), more likely to get craniectomy (2.1 vs. 1.2 %, p = 0.006), ventriculostomy (8.5 vs. 6.0 %, p < 0.001), intubation (32.2 vs. 25.9 %, p < 0.001), and tracheostomy (6.4 vs. 4.2 %, p < 0.001). Seizure patients had lower in-hospital mortality (24.3 vs. 28.0 %, p = 0.003). In a multivariable model incorporating patient and hospital level variables, seizures were associated with reduced odds of in-hospital death (OR = 0.62, 95 % CI 0.52-0.75). CONCLUSIONS: A secondary diagnosis of seizure after ICH was not associated with increased in-hospital death overall or in any of the pre-specified subgroups; however, there may be residual confounding by severity. These findings do not support a need for routine prophylactic anti-epileptic drug use after ICH.

Predictors of outcome in patients with spinal cord ischemia after open aortic repair.

INTRODUCTION: Spinal cord ischemia is a potentially devastating complication of thoracic aortic surgery. However, predictors of outcome have not been well characterized. The study objective was to generate a prognostic score that accurately stratifies patient outcomes, aiding in future management and planning. METHODS: A retrospective review of 224 consecutive open thoracic aortic surgeries identified patients with spinal cord ischemia, defined as changes on intraoperative somatosensory evoked potentials (SSEP) and/or paraparesis/paraplegia postoperatively. The outcome of interest was poor outcome, defined as death or discharge with a lower extremity motor score ≤40, indicating impaired ambulation. Demographic and clinical characteristics were tested in univariate analyses and significant factors were incorporated in multivariate modeling to determine independent predictors of poor outcome. RESULTS: Seventy-five patients were identified with spinal cord ischemia, of which 43(57 %) had poor outcomes including 28(37 %) that died prior to discharge. Factors associated with poor outcome in univariate analysis included absent lumbar CSF drain (p = 0.03), surgical repair that crossed the diaphragm (p = 0.002), permanent intraoperative SSEP change (p = 0.02), postoperative renal failure (p = 0.004), paraplegia (p = 0.001), and concomitant stroke (p = 0.04). In multivariable analysis, surgical repair crossing the diaphragm (OR 4.8, CI 1.4-16.7, p = 0.02), paraplegia (OR 4.5, CI 1.4-14.0, p = 0.01), and renal failure (OR 6.1, CI 1.7-21.2, p = 0.005) were independently associated with poor outcome. Patients with transient intraoperative neurophysiologic changes were least likely to have poor outcome when compared to patients with no or permanent SSEP changes, and those not monitored (p = 0.03). CONCLUSION: Development of spinal cord ischemia with thoracic aortic repair often leads to death or disability. Characteristics known at the time of event can accurately predict the likelihood of poor outcome.