Non-vitamin K oral anticoagulants (NOACs) are now widely used as alternatives to warfarin for stroke prevention in atrial fibrillation and management of venous thromboembolism. In clinical practice, ...there is still widespread uncertainty on how to manage patients on NOACs who bleed or who are at risk for bleeding. Clinical trial data related to NOAC reversal for bleeding and perioperative management are sparse, and recommendations are largely derived from expert opinion. Knowledge of time of last ingestion of the NOAC and renal function is critical to managing these patients given that laboratory measurement is challenging because of the lack of commercially available assays in the United States. Idarucizumab is available as an antidote to rapidly reverse the effects of dabigatran. At present, there is no specific antidote available in the United States for the oral factor Xa inhibitors. Prothrombin concentrate may be considered in life-threatening bleeding. Healthcare institutions should adopt a NOAC reversal and perioperative management protocol developed with multidisciplinary input.
Angiographic vasospasm frequently complicates subarachnoid hemorrhage and has been implicated in the development of delayed cerebral ischemia. Whether large-vessel narrowing adequately accounts for ...the critical reductions in regional cerebral blood flow underlying ischemia is unclear. We sought to clarify the relationship between angiographic vasospasm and regional hypoperfusion.
Twenty-five patients with aneurysmal subarachnoid hemorrhage underwent cerebral catheter angiography and 15O-positron emission tomographic imaging within 1 day of each other (median of 7 days after subarachnoid hemorrhage). Severity of vasospasm was assessed in each intracranial artery, whereas cerebral blood flow and oxygen extraction fraction were measured in 28 brain regions distributed across these vascular territories. We analyzed the association between vasospasm and perfusion and compared frequency of hypoperfusion (cerebral blood flow<25 mL/100 g/min) and oligemia (low oxygen delivery with oxygen extraction fraction≥0.5) in territories with versus without significant vasospasm.
Twenty-four percent of 652 brain regions were supplied by vessels with significant vasospasm. Cerebral blood flow was lower in such regions (38.6±12 versus 48.7±16 mL/100 g/min), whereas oxygen extraction fraction was higher (0.48±0.19 versus 0.37±0.14, both P<0.001). Hypoperfusion was seen in 46 regions (7%), but 66% of these were supplied by vessels with no significant vasospasm; 24% occurred in patients without angiographic vasospasm. Similarly, oligemia occurred more frequently outside territories with vasospasm.
Angiographic vasospasm is associated with reductions in cerebral perfusion. However, regional hypoperfusion and oligemia frequently occurred in territories and patients without vasospasm. Other factors in addition to large-vessel narrowing must contribute to critical reductions in perfusion.
Impaired oxygen delivery due to reduced cerebral blood flow is the hallmark of delayed cerebral ischemia following subarachnoid hemorrhage. Since anemia reduces arterial oxygen content, it further ...threatens oxygen delivery increasing the risk of cerebral infarction. Thus, subarachnoid hemorrhage may constitute an important exception to current restrictive transfusion practices, wherein raising hemoglobin could reduce the risk of ischemia in a critically hypoperfused organ. In this physiologic proof-of-principle study, we determined whether transfusion could augment cerebral oxygen delivery, particularly in vulnerable brain regions, across a broad range of hemoglobin values.
Prospective study measuring cerebral blood flow and oxygen extraction fraction using O-PET. Vulnerable brain regions were defined as those with baseline oxygen delivery less than 4.5 mL/100 g/min.
PET facility located within the Neurology/Neurosurgery ICU.
Fifty-two patients at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage with hemoglobin 7-13 g/dL.
Transfusion of one unit of RBCs over 1 hour.
Baseline hemoglobin was 9.7 g/dL (range, 6.9-12.9), and cerebral blood flow was 43 ± 11 mL/100 g/min. After transfusion, hemoglobin rose from 9.6 ± 1.4 to 10.8 ± 1.4 g/dL (12%; p < 0.001) and oxygen delivery from 5.0 (interquartile range, 4.4-6.6) to 5.5 mL/100 g/min (interquartile range, 4.8-7.0) (10%; p = 0.001); the response was comparable across the range of hemoglobin values. In vulnerable brain regions, transfusion resulted in a greater (16%) rise in oxygen delivery associated with reduction in oxygen extraction fraction, independent of Hgb level (p = 0.002 vs normal regions).
This study demonstrates that RBC transfusion improves cerebral oxygen delivery globally and particularly to vulnerable regions in subarachnoid hemorrhage patients at risk for delayed cerebral ischemia across a wide range of hemoglobin values and suggests that restrictive transfusion practices may not be appropriate in this population. Large prospective trials are necessary to determine if these physiologic benefits translate into clinical improvement and outweigh the risk of transfusion.
Background: Technological advances have diminished reliance on classroom attendance for mastering preclinical medical school course content, but nonattendance may have unintended consequence on the ...learning environment. Perceptions among educators and students regarding the value of attendance and implications of nonattendance have not been systematically studied. Purposes: The purpose of this study was to investigate differences in medical student and faculty attitudes regarding preclinical classroom attendance and the impact of nonattendance on educators and the learning environment. Methods: Using Internet-based surveys, we assessed attitudes about preclinical classroom attendance among medical students and teaching faculty at Washington University School of Medicine. Our primary hypothesis was that students would be less likely than faculty to place societal value on attendance and relate it to professionalism. Results: A total of 382 (79%) of 484 eligible students and 248 (64%) of 387 eligible faculty completed the survey. Both groups recognized a negative impact of poor attendance on faculty enthusiasm for teaching (students 83%, faculty 75%), but faculty were significantly more likely to endorse a negative impact on effectiveness of lectures (75% vs. 42%, p <.0001) and small-groups (92% vs. 76%, p <.0001) and a relationship between attendance and professionalism (88% vs. 68%, p <.0001). Students were significantly more likely to support free choice among learning opportunities (90% vs. 41%, p <.0001) including regularly missing class for research and community service activities (70% vs. 14%, p <.0001) and to consider lecture videos an adequate substitute for attendance (70% vs. 15%, p <.0001). Free-text responses suggested that students tended to view class-going primarily as a tool for learning factual material, whereas many faculty viewed it as serving important functions in the professional socialization process. Conclusions: In this single-center cohort, medical student and teaching faculty attitudes differed regarding the importance of classroom attendance and its relationship to professionalism, findings that were at least partially explained by differing expectations of the purpose of the preclinical classroom experience.
Progressive perihematomal cell death over 3 to 4 days has been described after experimental intracerebral hemorrhage (ICH). We investigated whether progressive perihematomal damage occurs in human ...subjects by measuring relative changes in regional cerebral glucose metabolism with (18)F-fluorordeoxyglucose (FDG) positron emission tomography at multiple time points during the first week after ICH.
Thirteen subjects with a median hematoma volume of 22 cm(3) were studied 1.0+/-0.3, 2.9+/-0.8, and 6.7+/-1.6 days after ICH. Normalized mean counts in 5 concentric annular 2-mm-thick perihematomal volumes-of-interest (VOIs) were compared to the initial study. Next, automated searches with 0.5 to 5.0 mL spherical VOIs identified maximum focal changes in normalized counts compared to the initial study.
No annular or focal decrease in perihematomal FDG uptake developed. Instead, FDG uptake significantly increased at session #2 in the first 3 2-mm annular VOIs (9.2%+/-14.2, 7.8%+/-11.3, 5.9%+/-9.0), returning to baseline at session #3. The VOI search identified focal regions of increased perihematomal FDG uptake relative to the contralateral control hemispheres in 6 subjects, which accounted for the annular increase.
Perihematomal glucose metabolism increased transiently in a subset of patients 2 to 4 days after acute ICH. These transient focal increases in glucose metabolism occurring in the brain after acute ICH demonstrate that there are ongoing processes in response to injury that last for days. Although further studies are needed to elucidate their pathophysiology, these processes may be indicative of a prolonged window for intervention to improve neurological outcome.
Background
The management of cerebral venous sinus thrombosis (CVT) is a common problem facing vascular neurologists. American Heart Association/American Stroke Association guidelines suggest the use ...of heparin followed by vitamin K antagonists (VKAs) for anticoagulation in CVT. In recent years, the evidence base has solidified for the use of non-vitamin K antagonist oral anticoagulants (NOACs) in lower extremity deep vein thrombosis. Because data supporting their use in CVT are limited, with the strongest evidence comprising one randomized controlled trial of dabigatran, we sought to review our experience with NOACs in the treatment of CVT at a tertiary care center to address efficacy and safety.
Methods
We retrospectively reviewed charts of all patients with CVT treated with an NOAC at our tertiary care facility in the years 2011–2019. We collected data on demographics, risk factors for CVT, clinical features at presentation, imaging results, anticoagulation regimen, bleeding complications, and disability at follow-up. We compared disability at follow-up and major hemorrhagic events with age-matched and sex-matched controls treated with VKAs over the same time period and with historical controls.
Results
We identified 29 patients with CVT treated with an NOAC, 27 of whom had follow-up within our system. NOACs that were used for treatment included apixaban (20 patients), rivaroxaban (6 patients) and dabigatran (1 patient). NOAC use was associated with stabilization of a clot or partial recanalization in 55.6% of patients and complete recanalization in 14.8% at a median follow-up time of 6 months. The median modified Rankin Score (mRS) at follow-up was 0, with one death. Three patients (11.1%) had major bleeding complications, including two with symptomatic worsening of intracranial hemorrhage. Comparisons of 27 age-matched and sex-matched controls treated with VKAs showed no significant differences in terms of partial recanalization (55.6% vs. 63.0%,
p
= 0.29), complete recanalization (14.8% vs. 25.9%,
p
= 0.73), mRS at follow-up (median 0 vs. 0,
p
= 0.23), or major bleeding (11.1% vs. 11.1%,
p
> 0.99). Comparisons with the historical International Study on Cerebral Vein and Dural Sinus Thrombosis cohort showed similar functional outcomes: 92.6% of patients treated with NOACs and 88.9% of patients treated with VKAs at the Washington University School of Medicine in St. Louis, as well as 86.2% of patients treated with VKAs in the historical study cohort, had mRS of 0–2 at follow-up (
p
= 0.60). Rates of major bleeding compared with this cohort were also similar (11.1% vs. 11.1% vs. 14.5%,
p
= 0.80).
Conclusions
The safety and efficacy results of NOAC use for CVT were similar to those for age-matched and sex-matched controls treated with VKAs, as well as historical published controls. Assessment of NOAC efficacy and safety in CVT in multicenter cohort studies and randomized controlled trials is warranted.
Abstract Purpose Cerebral blood flow (CBF) is reduced after severe traumatic brain injury (TBI) with considerable regional variation. Osmotic agents are used to reduce elevated intracranial pressure ...(ICP), improve cerebral perfusion pressure, and presumably improve CBF. Yet, osmotic agents have other physiologic effects that can influence CBF. We sought to determine the regional effect of osmotic agents on CBF when administered to treat intracranial hypertension. Materials and Methods In 8 patients with acute TBI, we measured regional CBF with positron emission tomography before and 1 hour after administration of equi-osmolar 20% mannitol (1 g/kg) or 23.4% hypertonic saline (0.686 mL/kg) in regions with focal injury and baseline hypoperfusion (CBF <25 mL per 100 g/min). Results The ICP fell (22.4 ± 5.1 to 15.7 ± 7.2 mm Hg, P = .007), and cerebral perfusion pressure rose (75.7 ± 5.9 to 81.9 ± 10.3 mm Hg, P = .03). Global CBF tended to rise (30.9 ± 3.7 to 33.1 ± 4.2 mL per 100 g/min, P = .07). In regions with focal injury, baseline flow was 25.7 ± 9.1 mL per 100 g/min and was unchanged; in hypoperfused regions (15% of regions), flow rose from 18.6 ± 5.0 to 22.4 ± 6.4 mL per 100 g/min ( P < .001). Osmotic therapy reduced the number of hypoperfused brain regions by 40% ( P < .001). Conclusion Osmotic agents, in addition to lowering ICP, improve CBF to hypoperfused brain regions in patients with intracranial hypertension after TBI.
A zone of hypoperfusion surrounding acute intracerebral hemorrhage (ICH) has been interpreted as regional ischemia. To determine if ischemia is present in the periclot area, the authors measured ...cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF) with positron emission tomography (PET) in 19 patients 5 to 22 hours after hemorrhage onset. Periclot CBF, CMRO2, and OEF were determined in a 1-cm-wide area around the clot. In the 16 patients without midline shift, periclot data were compared with mirror contralateral regions. All PET images were masked to exclude noncerebral structures, and all PET measurements were corrected for partial volume effect due to clot and ventricles. Both periclot CBF and CMRO2 were significantly reduced compared with contralateral values (CBF: 20.9 ± 7.6 vs. 37.0 ± 13.9 mL 100 g−1 min−1, P = 0.0004; CMRO2: 1.4 ± 0.5 vs. 2.9 ± 0.9 mL 100 g−1 min−1, P = 0.00001). Periclot OEF was less than both hemispheric OEF (0.42 ± 0.15 vs. 0.47 ± 0.13, P = 0.05; n = 19) and contralateral regional OEF (0.44 ± 0.16 vs. 0.51 ± 0.13, P = 0.05; n = 16). In conclusion, CMRO2 was reduced to a greater degree than CBF in the periclot region in acute ICH, resulting in reduced OEF rather than the increased OEF that occurs in ischemia. Thus, the authors found no evidence for ischemia in the periclot zone of hypoperfusion in acute ICH patients studied 5 to 22 hours after hemorrhage onset.
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