Inadvertent hypothermia after endovascular therapy is not associated with improved outcome in stroke due to anterior circulation large vessel occlusion.

BACKGROUND AND PURPOSE: Hypothermia may be neuroprotective in acute ischemic stroke. Patients with anterior circulation large vessel occlusion (acLVO) are frequently hypothermic after endovascular therapy (EVT). We sought to determine whether this inadvertent hypothermia is associated with improved outcome. METHODS: We extracted data of consecutive patients (January 2016 to May 2019) who received EVT for acLVO from our prospective EVT register of all patients screened for EVT at our tertiary stroke center. We assessed functional outcome at 3 months and performed multivariate analysis to calculate adjusted risk ratios (aRRs) for favorable outcome (modified Rankin Scale scores = 0-2) and mortality across patients who were hypothermic (<36°C) and patients who were normothermic (≥36°C to <37.6°C) after EVT. Moreover, we compared the frequency of complications between these groups. RESULTS: Among 837 patients screened, 416 patients received EVT for acLVO and fulfilled inclusion criteria (200 [48.1%] male, mean age = 76 ± 16 years, median National Institutes of Health Stroke Scale score = 16, interquartile range [IQR] = 12-20). Of these, 209 patients (50.2%) were hypothermic (median temperature = 35.2°C, IQR = 34.7-35.7) and 207 patients were normothermic (median temperature = 36.4°C, IQR = 36.1-36.7) after EVT. In multivariate analysis, hypothermia was not associated with favorable outcome (aRR = 0.99, 95% confidence interval [CI] = 0.75-1.31) and mortality (aRR = 1.18, 95% CI = 0.84-1.66). More hypothermic patients suffered from pneumonia (36.4% vs. 25.6%, p = 0.02) and bradyarrhythmia (52.6% vs. 16.4%, p < 0.001), whereas thromboembolic events were distributed evenly (5.7% vs. 6.8%, not significant). CONCLUSIONS: Inadvertent hypothermia after EVT for acLVO is not associated with improved functional outcome or reduced mortality but is associated with an increased rate of pneumonia and bradyarrhythmia in patients with acute ischemic stroke.

Acute kidney injury in patients with malignant middle cerebral artery infarction undergoing hyperosmolar therapy with mannitol.

PURPOSE: To assess the kidney safety profile of mannitol in patients with malignant middle cerebral artery (MCA) infarction. MATERIAL AND METHODS: We studied consecutive patients with malignant MCA infarction (01/2008-01/2018). Malignant MCA infarction was defined according to DESTINY criteria. We compared clinical endpoints including acute kidney injury (AKI; according to Kidney Disease: Improving Global Outcomes [KDIGO]) and dialysis between patients with and without mannitol. Multivariable model was built to explore predictor variables of AKI and in-hospital death. RESULTS: Overall, 219 patients with malignant MCA infarction were included. Mannitol was administered in 93/219 (42.5%) patients with an average dosage of 650 g (250-950 g). Patients treated with mannitol more frequently suffered from AKI (39.8% vs. 11.9%; p < 0.001) and required hemodialysis (7.5% vs. 0.8%; p = 0.01) than patients without mannitol. At discharge, more patients in the mannitol group had persistent AKI than control patients (23.7% vs. 6.4%, p < 0.001). In multivariable model, mannitol emerged as independent predictor of AKI (OR 5.02, 95%CI 2.36-10.69; p < 0.001). CONCLUSIONS: Acute kidney injury appears to be a frequent complication of hyperosmolar therapy with mannitol in patients with malignant MCA infarction. Given the lack of evidence supporting effectiveness of mannitol in these patients, its routine use should be carefully considered.

Endovascular therapy for anterior circulation large vessel occlusion in telestroke.

INTRODUCTION: Recent exploratory analysis suggested comparable outcomes among stroke patients undergoing endovascular therapy (EVT) for anterior circulation large vessel occlusion, whether selected via the telestroke network or admitted directly to an EVT-capable centre. We further studied the role of telemedicine in selection of ischaemic stroke patients potentially eligible for EVT. METHODS: We prospectively included consecutive ischaemic stroke patients with anterior circulation large vessel occlusion who underwent EVT at our neurovascular centre (January 2016 to March 2018). We compared safety and efficacy including symptomatic intracerebral haemorrhage (sICH), successful reperfusion (mTICI 2b/3), 90-day favourable outcome (mRS ≤ 2) and 90-day survival between patients transferred from telestroke hospitals and patients directly admitted. RESULTS: Of 280 potentially EVT-eligible patients, 72/129 (56%) telestroke and 91/151 (60%) direct admissions eventually underwent EVT (age 76 (66-82) years, median (interquartile range), 46% men, NIHSS score 17 (13-20)). Telestroke patients had larger pre-EVT infarct cores (ASPECTS: 7 (6-8) vs. 8 (7-9); p < 0.0001) and shorter door-to-groin puncture times (71 (56-84) vs. 101 (79-133) min; p < 0.0001) than directly admitted patients. sICH (2.8% vs. 1.1%; p = 0.58), successful reperfusion (81% vs. 77%; p = 0.56), 90-day favourable outcome (25% vs. 29%; p = 0.65) and 90-day survival (73% vs. 67%; p = 0.39) rates were comparable among telestroke and direct admissions. DISCUSSION: Our data underpins the important role of telemedicine in identifying acute ischaemic stroke patients lacking immediate access to EVT-capable stroke centres. Stroke patients selected via telemedicine and those directly admitted had comparable chances of favourable outcomes after EVT for large vessel occlusion.

Universal laboratory testing for SARS-CoV-2 in hyperacute stroke during the COVID-19 pandemic.

OBJECTIVE: Stroke patients are thought to be at increased risk of Coronavirus Disease 2019 (COVID-19). To evaluate yield of universal laboratory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute stroke patients and its impact on hyperacute stroke care. METHODS: Between weeks 14 and 18 in 2020, a protected code stroke protocol including infection control screening and laboratory testing for SARS-CoV-2 was prospectively implemented for all code stroke patients upon arrival to the emergency department. If infection control screen was positive, patients received protective hygienic measures and laboratory test results were available within four hours from testing. In patients with negative screen, laboratory results were available no later than the next working day. Door-to-imaging times of patients treated with thrombolysis or thrombectomy were compared with those of patients treated during the preceding weeks 1 to 13 in 2020. RESULTS: During the 4-weeks study period, 116 consecutive code stroke patients underwent infection control screen and laboratory testing for SARS-CoV-2. Among 5 (4.3%) patients whose infection control screen was positive, no patient was tested positive for SARS-CoV-2. All patients with negative infection control screens had negative test results. Door-to-imaging times of patients treated with thrombolysis and/or thrombectomy were not different to those treated during the preceding weeks (12 [9-15] min versus 13 [11-17] min, p = 0.24). CONCLUSIONS: Universal laboratory testing for SARS-CoV-2 provided useful information on patients' infection status and its implementation into a protected code stroke protocol did not adversely affect hyperacute stroke care.

Association of Hypertensive Intracerebral Hemorrhage with Left Ventricular Hypertrophy on Transthoracic Echocardiography.

INTRODUCTION: Arterial hypertension is the most frequent cause for spontaneous intracerebral hemorrhage (sICH) and may also cause left ventricular hypertrophy (LVH). We sought to analyze whether hypertensive sICH etiology is associated with LVH. METHODS: We analyzed consecutive patients with sICH who were admitted to our tertiary stroke center during a four-year period and underwent transthoracic echocardiography (TTE) as part of the diagnostic work-up. We defined hypertensive sICH as typical localization of hemorrhage in patients with arterial hypertension and no other identified sICH etiology. We defined an increased end-diastolic interventricular septal wall thickness of ≥11 mm on TTE as a surrogate parameter for LVH. RESULTS: Among 395 patients with sICH, 260 patients (65.8%) received TTE as part of their diagnostic work-up. The median age was 71 years (interquartile range (IQR) 17), 160 patients (61.5%) were male, the median baseline National Institute of Health Stroke Scale (NIHSS) score was 8 (IQR 13). Of these, 159 (61.2%) patients had a hypertensive sICH and 156 patients (60%) had LVH. In univariable (113/159 (71.1%) vs. 43/101 (42.6%); odds ratio (OR) 3.31; 95% confidence interval (CI95%) 1.97-5.62); and multivariable (adjusted OR 2.95; CI95% 1.29-6.74) analysis, hypertensive sICH was associated with LVH. CONCLUSIONS: In patients with sICH, LVH is associated with hypertensive bleeding etiology. Performing TTE is meaningful for diagnosis of comorbidities and clarification of bleeding etiology in these patients. Future studies should include long-term outcome parameters and assess left ventricular mass as main indicator for LVH.

Safety of inter-hospital transfer of patients with acute ischemic stroke for evaluation of endovascular thrombectomy.

Stroke networks facilitate access to endovascular treatment (EVT) for patients with ischemic stroke due to large vessel occlusion. In this study we aimed to determine the safety of inter-hospital transfer and included all patients with acute ischemic stroke who were transferred within our stroke network for evaluation of EVT between 06/2016 and 12/2018. Data were derived from our prospective EVT database and transfer protocols. We analyzed major complications and medical interventions associated with inter-hospital transfer. Among 615 transferred patients, 377 patients (61.3%) were transferred within our telestroke network and had transfer protocols available (median age 76 years [interquartile range, IQR 17], 190 [50.4%] male, median baseline NIHSS score 17 [IQR 8], 246 [65.3%] drip-and-ship i.v.-thrombolysis). No patient suffered from cardio-respiratory failure or required emergency intubation or cardiopulmonary resuscitation during the transfer. Among 343 patients who were not intubated prior departure, 35 patients (10.2%) required medical interventions during the transfer. The performance of medical interventions was associated with a lower EVT rate and higher mortality at three months. In conclusion, the transfer of acute stroke patients for evaluation of EVT was not associated with major complications and transfer-related medical interventions were required in a minority of patients.

Association of Anesthetic Exposure Time With Clinical Outcomes After Endovascular Therapy for Acute Ischemic Stroke.

Background: The optimal sedative regimen with general anesthesia (GA) or conscious sedation for patients undergoing endovascular therapy (EVT) remains controversial. Apart from sedative regimen, the duration of anesthetic exposure may affect clinical outcomes. We aimed to determine whether there is an association between anesthetic exposure time and clinical outcomes in mechanically ventilated stroke patients undergoing EVT for large vessel occlusion. Methods: This was an observational study of consecutive ischemic stroke patients who underwent EVT for anterior circulation large vessel occlusion under GA from January 2016 to March 2018. To minimize confounding by indication, we restricted our analysis to patients whose anesthetic exposure lasted <72 h. Multivariable logistic regression modeling adjusted for covariates was employed to evaluate whether 90-days independent functional outcome (defined as modified Rankin Scale scores 0-2) and 90-days survival could be predicted by anesthetic exposure time. Results: During the study period, 138 patients with ischemic stroke who underwent EVT received GA and fulfilled our study criteria: median age was 77 years (interquartile range, 65-82); 46.4% were men; median NIHSS score was 18 (15-21), median ASPECT score was 7 (6-8). Median duration of GA was 5.4 (2.5-19.7) h. Logistic regression modeling revealed an independent association between duration of anesthetic exposure and both 90-days independent functional outcome (p = 0.034) and 90-days survival (p = 0.011). Each additional 15-min of anesthetic exposure decreased the likelihood of achieving an independent functional outcome at 90 days by 1.5% and of being alive at 90 days by 1.0%. Conclusion: Our data promotes the notion that ischemic stroke patients who require peri-interventional GA for EVT should be extubated as soon as possible after the procedure.

Misjudgment of pre-stroke functional status contradicts beneficial outcomes after endovascular therapy for large vessel occlusion.

Endovascular therapy (EVT) trials enrolled ischemic stroke patients with good pre-stroke functional status. However, this information needed for rapid decision-making is commonly lacking in clinical practice. We hypothesized that initial misjudgment of pre-stroke functional status attenuates clinical outcomes of EVT. Data were derived from our prospective registry of ischemic stroke patients undergoing EVT for anterior circulation large vessel occlusion (01/2016-12/2017). Considering all information accumulated during hospital course, pre-stroke modified Rankin scale (mRS) was independently re-assessed and compared with pre-EVT assessments. Misjudgment was defined as any difference in mRS categories between first- and second-look assessments. Multivariable model was built to adjust for confounding variables of unfavorable outcome (mRS 3-6) and death at 90 days. Overall, we studied 217 patients: median age 75 years (IQR 64-81), 54% women, median NIHSS 17 (12-20) points. Second-look assessment of pre-stroke mRS revealed 73 (34%) cases initially being misjudged by ≥ 1 category and 17 (8%) by ≥ 2 categories. None of the second-look mRS assessments resulted in a lower mRS category than initially rated. Patients whose pre-stroke mRS score was misjudged prior to EVT showed more frequently unfavorable outcome (62/73 [84.9%] vs. 94/144 [65.3%], p = 0.002) or were deceased (30/73 [41.1%] vs. 25/144 [17.4%], p < 0.001) at 90 days than patients with consistent mRS assessments. Moreover, unfavorable outcomes occurred in nearly all patients whose initial mRS was misjudged by ≥ 2 categories (mRS 3-6: 17/17 [100%]; death: 14/17 [82.4%]; p < 0.001). In conclusion, thorough pre-EVT assessment of pre-stroke functional status appears decisive for proper selection of EVT candidates.

Low Diagnostic Yield of Routine Cerebrospinal Fluid Analysis in Juvenile Stroke.

Background: The diagnostic value of cerebrospinal fluid (CSF) analysis in juvenile stroke, i.e., stroke in young adult patients, is not well studied. We sought to determine the therapeutic impact of routine CSF-analysis in young adults with acute ischemic stroke or transient ischemic attack (TIA). Methods: We abstracted data from patients with acute cerebral ischemia aged 18-45 years who were consecutively admitted to our stroke center between 01/2008 and 12/2015. We routinely performed CSF-analysis in patients with hitherto unknown stroke etiology after complete diagnostic work up. We assessed the frequency and underlying causes of abnormal CSF-findings and their impact on secondary stroke prevention therapy. Results: Among 379 patients (median [IQR:IQR3-IQR1] age 39 [10:43-33] years, 48% female) with acute ischemic stroke (n = 306) or TIA (n = 73), CSF analysis was performed in 201 patients (53%). Of these, 25 patients (12.4 %) had CSF pleocytosis (leucocyte cell count ≥ 5 Mpt/L), that was rated as non-specific (e.g., traumatic lumbar puncture, reactive pleocytosis) in 22 patients. Only 3 patients (1.5% of all patients who underwent CSF-analysis) with CSF-pleocytosis had specific CSF-findings that were related to stroke etiology and affected secondary stroke prevention therapy. Imaging findings had already suggested cerebral vasculitis in two of these patients. Conclusions: The diagnostic yield of routine CSF-analysis in juvenile stroke was remarkably low in our study. Our data suggest that CSF-analysis should only be performed if further findings raise the suspicion of cerebral vasculitis.

Standardized use of novel oral anticoagulants plasma level thresholds in a new thrombolysis decision making protocol.

Acute ischemic stroke (AIS) patients receiving non-vitamin-K antagonist oral anticoagulants (NOAC) are commonly excluded from thrombolytic therapy, as interpretation of coagulation tests remains unclear. We aimed to investigate the applicability of a novel institutional protocol for thrombolysis based on current expert recommendations and NOAC specific coagulation assessment. We included hospitalized AIS patients receiving NOAC for at least 24 h and consecutive AIS patients not receiving NOAC into a prospective study. We performed standard coagulation tests and specific tests for dabigatran, rivaroxaban and apixaban plasma levels. We studied 65 patients: mean age 72 ± 13 years, 30 (46 %) male, median NIHSS score 3 (IQR 6). Fifteen (23 %) were on NOAC treatment (5 dabigatran, 5 rivaroxaban, and 5 apixaban, respectively) and 50 (77 %) were not. In patients without NOAC, dabigatran was not detectable (0 ng/ml), and plasma levels of rivaroxaban (median: 10.0 ng/ml, IQR 7.0) and apixaban (7.2 ng/ml, IQR 6.7) were below our lower thresholds that allow thrombolysis. In patients with dabigatran pre-treatment, trough levels (58.0 ng/ml, IQR 143.0) were below our upper threshold that would allow thrombolysis in 3/5 patients. In patients receiving rivaroxaban, trough level (68.0 ng/ml, IQR 64.0) was below our predefined upper thresholds that would allow thrombolysis in 4/5 patients. In all patients on apixaban, trough level was above our predefined threshold of 40 ng/ml that precludes thrombolysis (98.2 ng/ml, IQR 84.3). Predefined thresholds of NOAC plasma levels in the decision of thrombolysis in NOAC treated AIS patients might supplement routine coagulation tests and should be validated in a larger study population.

Continuous non-invasive monitoring of tidal volumes by measurement of tidal impedance in neonatal piglets.

BACKGROUND: Electrical Impedance measurements can be used to estimate the content of intra-thoracic air and thereby give information on pulmonary ventilation. Conventional Impedance measurements mainly indicate relative changes, but no information concerning air-volume is given. The study was performed to test whether a 3-point-calibration with known tidal volumes (VT) during conventional mechanical ventilation (CMV) allows subsequent calculation of VT from total Tidal-Impedance (tTI) measurements using Quadrant Impedance Measurement (QIM). In addition the distribution of TI in different regions of the thorax was examined. METHODOLOGY AND PRINCIPAL FINDINGS: QIM was performed in five neonatal piglets during volume-controlled CMV. tTI values at three different VT (4, 6, 8 ml/kg) were used to establish individual calibration curves. Subsequently, each animal was ventilated with different patterns of varying VT (2-10 ml/kg) at different PEEP levels (0, 3, 6, 9, 12 cmH(2)O). VT variation was repeated after surfactant depletion by bronchoalveolar lavage. VT was calculated from tTI values (VT(calc)) and compared to the VT delivered by the ventilator (VT(PNT)). Bland-Altman analysis revealed good agreement between VT(calc) and VT(PNT) before (bias -0.08 ml; limits of agreement -1.18 to 1.02 ml at PEEP = 3 cmH(2)O) and after surfactant depletion (bias -0.17 ml; limits of agreement -1.57 to 1.22 ml at PEEP = 3 cmH(2)O). At higher PEEP levels VT(calc) was lower than VT(PNT), when only one fixed calibration curve (at PEEP 3 cmH(2)O) was used. With a new calibration curve at each PEEP level the method showed similar accuracy at each PEEP level. TI showed a homogeneous distribution over the four assessed quadrants with a shift toward caudal regions of the thorax with increasing VT. CONCLUSION: Tidal Impedance values could be used for precise and accurate calculation of VT during CMV in this animal study, when calibrated at each PEEP level.