Anticoagulation Holiday: Resumption of Direct Oral Anticoagulants for Atrial Fibrillation in Patients with Index Traumatic Intracranial Hemorrhage.

Background: The optimal time to restart direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF) after traumatic intracranial hemorrhage (tICH) is unknown. Physicians must weigh the risk of recurrent hemorrhage against ischemic stroke. We investigated rates of stroke while holding anticoagulation, hemorrhage after anticoagulation resumption, and factors associated with the decision to restart anticoagulation. Methods: Patients presenting to our level I trauma center for tICH while on a DOAC for NVAF were retrospectively reviewed over 2 years. Age, sex, DOAC use, antiplatelet use, congestive heart failure, hypertension, age, diabetes, previous stroke, vascular disease, sex score for stroke risk in NVAF, injury mechanism, bleeding pattern, Injury Severity Score, use of a reversal agent, Glasgow Coma Scale at 24 hours, hemorrhage expansion, neurosurgical intervention, Morse Fall Risk, DOAC restart date, rebleed events, and ischemic stroke were recorded to study rates of recurrent hemorrhage and stroke, and factors that influenced the decision to restart anticoagulation. Results: Twenty-eight patients sustained tICH while on a DOAC. Fall was the most common mechanism (89.3%), and subdural hematoma was the predominant bleeding pattern (60.7%). Of the 25 surviving patients, 16 patients (64%) restarted a DOAC a median 29.5 days after tICH. One patient had recurrent hemorrhage after resuming anticoagulation. One patient had an embolic stroke after 118 days off anticoagulation. Age >80, Injury Severity Score ≥16, and expansion of tICH influenced the decision to indefinitely hold anticoagulation. Conclusion: The low stroke rate observed in this study suggests that holding DOACs for NVAF for 1 month is sufficient to reduce the risk of stroke after tICH. Additional data are required to determine optimal restart timing.

Persistent Blunting of Penumbral Leukocyte Mobilization by Beta Blockade Administered for Two Weeks After Traumatic Brain Injury.

INTRODUCTION: Beta-blockers (BB) after traumatic brain injury (TBI) accelerate cognitive recovery weeks after injury. BBs also inhibit leukocyte (LEU) mobilization to the penumbral blood brain barrier (BBB) 48-h after TBI. It is unclear whether the latter effects persist longer and accompany the persistent cognitive improvement. We hypothesized that 2 wk of BB after TBI reduce penumbral BBB leukocyte-endothelial interactions. METHODS: Thirty CD1 mice underwent TBI (controlled cortical impact, CCI: 6 m/s velocity, 1 mm depth, 3 mm diameter) or sham craniotomy followed by i.p. saline (NS) or propranolol (1, 2, 4 mg/kg) every 12 h for 14 d. On day 14, in vivo pial intravital microscopy visualized endothelial-LEU interactions and BBB microvascular leakage. Day 14 Garcia neurological test scores and animal weights were compared to preinjury levels reflecting concurrent clinical recovery. RESULTS: LEU rolling was greatest in CCI + NS when compared to sham (P = 0.03). 4 mg/kg propranolol significantly reduced postCCI LEU rolling down to uninjured sham levels (P = 0.03). LEU adhesion and microvascular permeability were not impacted at this time interval. Untreated injured animals (CCI + NS) scored lower Garcia neurological test and greater weight loss recovery at day 14 when compared to preinjury (P < 0.05). Treatment with higher doses of propranolol (2, 4 mg/kg), improved weight loss recovery (P < 0.001). CONCLUSIONS: LEU rolling alone, was influenced by BB therapy 14 d after TBI suggesting that certain penumbral neuroinflammatory cellular effects of BB therapy after TBI persist up to 2 wk after injury potentially explaining the pervasive beneficial effects of BBs on learning and memory.

Application of a TEG-Platelet Mapping Algorithm to Guide Reversal of Antiplatelet Agents in Adults with Mild-to-Moderate Traumatic Brain Injury: An Observational Pilot Study.

BACKGROUND: Traumatic intracranial hemorrhages expand in one third of cases, and antiplatelet medications may exacerbate hematoma expansion. However, the reversal of an antiplatelet effect with platelet transfusion has been associated with harm. We sought to determine whether a thromboelastography platelet mapping (TEG-PM)-guided algorithm could limit platelet transfusion in patients with hemorrhagic traumatic brain injury (TBI) prescribed antiplatelet medications without a resultant clinically significant increase in hemorrhage volume, late hemostatic treatments, or delayed operative intervention. METHODS: A total of 175 consecutive patients with TBI were admitted to our university-affiliated, level I trauma center between March 2016 and December 2019: 54 preintervention patients (control) and 121 patients with TEG-PM (study). After exclusion for anticoagulant administration, availability of neuroimaging and emergent neurosurgery, 62 study patients and 37 control patients remained. Intervention consisted of administration of desmopressin (DDAVP) for nonsurgical patients with significant inhibition at the arachidonic acid or adenosine diphosphate receptor sites. For surgical patients with significant inhibition, dual therapy with DDAVP and platelet transfusion was employed. Study patients were compared with a group of historical controls, which were identified from a prospectively maintained registry and typically treated with empiric platelet transfusion. RESULTS: Median age was 75 years (interquartile range 85-67) and 77 years (interquartile range 81-65) in the TEG-PM and control patient groups, respectively. Admission hemorrhage volumes were similar (10.7 cm3 [20.1] in patients with TEG-PM vs. 14.1 cm3 [19.7] in controls; p = 0.41). There were no significant differences in admission Glasgow Coma Scale, mechanism of trauma, or baseline comorbidities. A total of 57% of controls versus 10% of patients with TEG-PM (p < 0.001) were transfused platelets; 52% of intervention patients and 0% controls were treated with DDAVP. Expansion hemorrhage volumes were not significantly different (14.0 cm3 [20.2] patients with TEG-PM versus 13.6 cm3 [23.7] controls; p = 0.93). There was no significant difference in rates of clinical deterioration, delayed neurosurgical intervention, or late platelet transfusion between groups. CONCLUSIONS: Among patients with hemorrhagic TBI prescribed preinjury antiplatelet therapy, our study suggests that the use of a TEG-PM algorithm may reduce platelet transfusions without a concurrent increase in clinically significant hematoma expansion. Further study is required to prove a causative relationship.

Beta blockade in TBI: Dose-dependent reductions in BBB leukocyte mobilization and permeability in vivo.

BACKGROUND: Traumatic brain injury (TBI) is accompanied by a hyperadrenergic catecholamine state that can cause penumbral neuroinflammation. Prospective human studies demonstrate improved TBI survival with beta blockade (bb), although mechanisms remain unclear. We hypothesized that deranged post-TBI penumbral blood brain barrier (BBB) leukocyte mobilization and permeability are improved by bb. METHODS: CD1 male mice (n = 64) were randomly assigned to severe TBI-controlled cortical impact: 6 m/s velocity, 1 mm depth, 3 mm diameter-or sham craniotomy, and IP injection of either saline or propranolol (1, 2, or 4 mg/kg) every 12 hours for 2 days. At 48 hours, in vivo pial intravital microscopy visualized live endothelial-leukocyte (LEU) interactions and BBB microvascular leakage. Twice daily clinical recovery was assessed by regaining of lost body weight and the Garcia Neurological Test (motor, sensory, reflex, balance assessments). Brain edema was determined by hemispheric wet-to-dry ratios. RESULTS: Propranolol after TBI reduced both in vivo LEU rolling and BBB permeability in a dose-dependent fashion compared with no treatment (p < 0.001). Propranolol reduced cerebral edema (p < 0.001) and hastened recovery of lost body weight at 48 hours (p < 0.01). Compared with no treatment (14.9 ± 0.2), 24-hour Garcia Neurologic Test scores were improved with 2 (15.8 ± 0.2, p = 0.02) and 4 (16.1 ± 0.1, p = 0.001) but not with 1 mg/kg propranolol. CONCLUSION: Propranolol administration reduces post-TBI LEU mobilization and microvascular permeability in the murine penumbral neurovasculature and leads to reduced cerebral edema. This is associated with hastened recovery of post-TBI weight loss and neurologic function with bb treatment. Dose-dependent effects frame a mechanistic relationship between bb and improved human outcomes after TBI.

Association of External Ventricular Drain Wean Strategy with Shunt Placement and Length of Stay in Subarachnoid Hemorrhage: A Prospective Multicenter Study.

BACKGROUND: Survivors of aneurysmal subarachnoid hemorrhage (SAH) face a protracted intensive care unit (ICU) course and are at risk for developing refractory hydrocephalus with the need for a permanent ventriculoperitoneal shunt (VPS). Management of the external ventricular drain (EVD) used to provide temporary cerebrospinal fluid diversion may influence the need for a VPS, ICU length of stay (LOS), and drain complications, but the optimal EVD management approach is unknown. Therefore, we sought to determine the effect of EVD discontinuation strategy on VPS rate. METHODS: This was a prospective multicenter observational study at six neurocritical care units in the United States. The target population included adults with suspected aneurysmal SAH who required an EVD. Patients were preassigned to rapid or gradual EVD weans based on their treating center. The primary outcome was the rate of VPS placement. Secondary outcomes were EVD duration, ICU LOS, hospital LOS, and drain complications. RESULTS: A rapid EVD wean protocol was associated with a lower rate of VPS placement, including a delayed posthospitalization shunt, in an adjusted Cox proportional analysis (hazard ratio 0.52 [p = 0.041]) and adjusted logistic regression model (odds ratio 0.43 [95% confidence interval 0.18-1.03], p = 0.057). A rapid wean was also associated with 2.1 fewer EVD days (p = 0.007) and saved an estimated 2.5 ICU days (p = 0.049), as compared with a gradual wean protocol. There were fewer nonfunctioning EVDs in the rapid group (odds ratio 0.32 [95% confidence interval 0.11-0.92]). Furthermore, we found that the time to first wean and the number of weaning attempts were important independent covariates that affected the likelihood of receiving a VPS and the duration of ICU admission. CONCLUSIONS: A rapid EVD wean was associated with decreased rates of VPS placement, decreased ICU LOS, and decreased drain complications in survivors of aneurysmal SAH. These findings suggest that a randomized multicentered controlled study comparing rapid vs. gradual EVD weaning protocols is justified.

Standardized Transfer Process for a Neurointensive Care Unit and Assessment of Patient Bounceback.

BACKGROUND: Patients who require readmission to an intensive care unit (ICU) after transfer to a lower level of care ("bounceback") suffer from increased mortality and longer hospital stays. We aimed to create a multifaceted standardized transfer process for patients moving from the neurointensive care unit (neuro-ICU) to a lower level of care. We hypothesized that this process would lead to improvement in provider-rated safety and a decreased rate of bouncebacks to the neuro-ICU after transfer. METHODS: The study took place at the Hospital of the University of Pennsylvania from October 2018 to October 2020. A standardized five-step transfer process was created and implemented for transferring patients from the neuro-ICU to a lower level of care. Patient care providers completed a survey before and after implementation of the protocol to assess a variety of components related to safety concerns when transferring patients. The rate of bouncebacks pre and post intervention was calculated by using a two-sample Wilcoxon rank-sum test, and disposition at discharge was calculated by using Fisher's exact test. RESULTS: Of the 1176 total patient transfers out of the neuro-ICU, 29 patients bounced back within 48 h. The average age of patients who bounced back was 63.3 years old, with a similar distribution among men and women. The most common reason for bounceback was respiratory distress, followed by cardiac arrhythmia, stroke, and sepsis. Implementation of the standardized process led to a decrease in provider-rated concern of overall safety (5 to 3, p = 0.008). There was improvement in transfer delays due to bed availability (3 to 4.5, p = 0.020), identification of high-risk patients (5 to 6, p = 0.021), patient assignment to the appropriate level of care (5 to 6, p = 0.019), and use of the electronic medical record handoff indicator (5 to 6, p = 0.003). There was no statistically significant difference in terms of patient bounceback rate after implementation of the process (2.4% vs. 2.5%, p = 1.00) or patient disposition at discharge (p = 0.553). CONCLUSIONS: Patients who bounceback to the neuro-ICU within 48 h had an increased length of hospital stay, had an increased length of ICU stay, and were more likely to be intubated for more than 96 h. Implementation of a standardized five-step transfer process from the neuro-ICU to a lower level of care resulted in improvement in multiple provider-rated safety outcomes and identification of high-risk patients but led to no difference in the patient bounceback rate or patient disposition at discharge.

Use of Thromboelastography in the Evaluation and Management of Patients With Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Traumatic brain injury is associated with coagulopathy that increases mortality risk. Viscoelastic hemostatic assays such as thromboelastography (Haemonetics SA, Signy, Switzerland) provide rapid coagulopathy assessment and may be particularly useful for goal-directed treatment of traumatic brain injury patients. We conducted a systematic review to assess thromboelastography in the evaluation and management of coagulopathy in traumatic brain injury patients. DATA SOURCES: MEDLINE, PubMed Central, Embase, and CENTRAL. STUDY SELECTION: Clinical studies of adult patients with traumatic brain injury (isolated or polytrauma) who were assessed by either standard thromboelastography or thromboelastography with platelet mapping plus either conventional coagulation assays or platelet function assays from January 1999 to June 2021. DATA EXTRACTION: Demographics, injury mechanism and severity, diagnostic, laboratory data, therapies, and outcome data were extracted for analysis and comparison. DATA SYNTHESIS: Database search revealed 1,169 sources; eight additional articles were identified by the authors. After review, 31 publications were used for qualitative analysis, and of these, 16 were used for quantitative analysis. Qualitative and quantitative analysis found unique patterns of thromboelastography and thromboelastography with platelet mapping parameters in traumatic brain injury patients. Patterns were distinct compared with healthy controls, nontraumatic brain injury trauma patients, and traumatic brain injury subpopulations including those with severe traumatic brain injury or penetrating traumatic brain injury. Abnormal thromboelastography K-time and adenosine diphosphate % inhibition on thromboelastography with platelet mapping are associated with decreased survival after traumatic brain injury. Subgroup meta-analysis of severe traumatic brain injury patients from two randomized controlled trials demonstrated improved survival when using a viscoelastic hemostatic assay-guided resuscitation strategy (odds ratio, 0.39; 95% CI, 0.17-0.91; p = 0.030). CONCLUSIONS: Thromboelastography and thromboelastography with platelet mapping characterize coagulopathy patterns in traumatic brain injury patients. Abnormal thromboelastography profiles are associated with poor outcomes. Conversely, treatment protocols designed to normalize abnormal parameters may be associated with improved traumatic brain injury patient outcomes. Current quality of evidence in this population is low; so future efforts should evaluate viscoelastic hemostatic assay-guided hemostatic resuscitation in larger numbers of traumatic brain injury patients with specific focus on those with traumatic brain injury-associated coagulopathy.

Early mobilization in neurocritical care patients.

PURPOSE OF REVIEW: To examine the potential benefits of early mobilization in neurocritically ill patients and to summarize the recent evidence for and against early mobilization. RECENT FINDINGS: Early ICU mobilization in medically critically ill patients may decrease ICU and hospital length of stay, increase discharge-to-home, and reduce medical costs. Whether these benefits apply to neurologically critically ill patients remains unclear, as neuro ICU patients are often excluded from trials of early mobility. Neurocritically ill patients may present with hemodynamic instability, acute hemiplegia, altered consciousness and visual field deficits which complicate mobilization, or have cerebral ischemia, which may be exacerbated when upright or active. Results of early mobilization in neurocritical care are mixed. For example, a randomized trial in acute ischemic stroke demonstrated that very early mobilization was associated with worse outcomes. However, many smaller intervention trials in neurocritical care demonstrate safety and feasibility with early mobilization, including those in patients with invasive devices, for example, external ventricular drains. SUMMARY: Given successes in other critically ill populations, early mobility of neurocritically ill patients may be warranted. However, caution should be exercised given the results in acute stroke trials. In addition, before routine use, the character, quality, dose, duration, and timing of early mobilization therapies requires further definition.

Evidence-Based Management of External Ventricular Drains.

PURPOSE OF REVIEW: The optimal management of external ventricular drains (EVD) in the setting of acute brain injury remains controversial. Therefore, we sought to determine whether there are optimal management approaches based on the current evidence. RECENT FINDINGS: We identified 2 recent retrospective studies on the management of EVDs after subarachnoid hemorrhage (SAH) which showed conflicting results. A multicenter survey revealed discordance between existing evidence from randomized trials and actual practice. A prospective study in a post-traumatic brain injury (TBI) population demonstrated the benefit of EVDs but did not determine the optimal management of the EVD itself. The recent CLEAR trials have suggested that specific positioning of the EVD in the setting of intracerebral hemorrhage with intraventricular hemorrhage may be a promising approach to improve blood clearance. Evidence on the optimal management of EVDs remains limited. Additional multicenter prospective studies are critically needed to guide approaches to the management of the EVD.

Safety and Feasibility of Early Mobilization in Patients with Subarachnoid Hemorrhage and External Ventricular Drain.

BACKGROUND/OBJECTIVE: In November 2014, our Neurointensive Care Unit began a multi-phased progressive early mobilization initiative for patients with subarachnoid hemorrhage and an external ventricular drain (EVD). Our goal was to transition from a culture of complete bed rest (Phase 0) to a physical and occupational therapy (PT/OT)-guided mobilization protocol (Phase I), and ultimately to a nurse-driven mobilization protocol (Phase II). We hypothesized that nurses could mobilize patients as safely as an exclusively PT/OT-guided approach. METHODS: In Phase I, patients were mobilized only with PT/OT at bedside; no independent time out of bed occurred. In Phase II, nurses independently mobilized patients with EVDs, and patients could remain out of bed for up to 3 h at a time. Physical and occupational therapists continued routine consultation during Phase II. RESULTS: Phase II patients were mobilized more frequently than Phase I patients [7.1 times per ICU stay (± 4.37) versus 3.0 times (± 1.33); p = 0.02], although not earlier [day 4.9 (± 3.46) versus day 6.0 (± 3.16); p = 0.32]. All Phase II patients were discharged to home PT services or acute rehabilitation centers. No patients were discharged to skilled nursing or long-term acute care hospitals, versus 12.5% in Phase I. In a multivariate analysis, odds of discharge to home/rehab were 3.83 for mobilized patients, independent of age and severity of illness. Other quality outcomes (length of stay, ventilator days, tracheostomy placement) between Phase I and Phase II patients were similar. No adverse events were attributable to early mobilization. CONCLUSIONS: Nurse-driven mobilization for patients with EVDs is safe, feasible, and leads to more frequent ambulation compared to a therapy-driven protocol. Nurse-driven mobilization may be associated with improved discharge disposition, although exact causation cannot be determined by these data.

Relative Deficiency of Plasma A Disintegrin and Metalloprotease with Thrombospondin Type 1 Repeats 13 Activity and Elevation of Human Neutrophil Peptides in Patients with Traumatic Brain Injury.

Traumatic microvascular injury (tMVI) is a universal endophenotype of traumatic brain injury (TBI) that is responsible for significant neurological morbidity and mortality. The mechanism underlying tMVI is not fully understood. The present study aims to determine plasma levels of von Willebrand factor (VWF), a disintegrin and metalloprotease with thrombospondin type 1 repeats (ADAMTS) 13 activity, and human neutrophil peptides (HNP) 1-3 and to correlate these biomarkers with functional outcomes after moderate-severe TBI. Thirty-one consecutive TBI patients (Glasgow Coma Scale [GCS] range, 3-12) were enrolled into the study between February 2010 and November 2014. Blood samples were collected on 0, 1, 2, 3, and 5 days after admission and analyzed for plasma levels of VWF antigen (VWFAg), collagen-binding activity (VWFAc), ADAMTS13 activity, and HNP1-3 proteins. Mean values of plasma VWFAg, VWFAc, and HNP1-3 were significantly increased in TBI patients compared to those in healthy controls (n = 30). Conversely, mean plasma values of ADAMTS13 activity in TBI patients were significantly decreased during the first 2 days after admission. This resulted in a dramatic reduction in the ratio of ADAMTS13 activity to VWFAg or ADAMTS13 to VWFAc in all 5 post-TBI days. Cluster analysis demonstrated that high median plasma levels of VWFAg and HNP1-3 were observed in the cluster with a high mortality rate. These results demonstrate that a relative deficiency of plasma ADAMTS13 activity, resulting from activation of neutrophils and endothelium, may contribute to the formation of microvascular thrombosis and mortality after moderate-severe TBI.

Education Research: Variation in priorities for neurocritical care education expressed across role groups.

OBJECTIVE: To define expectations for neurocritical care (NCC) core competencies vs competencies considered within the domain of other subspecialists. METHODS: An electronic survey was disseminated nationally to NCC nurses, physicians, fellows, and neurology residents through Accreditation Council for Graduate Medical Education neurology residency program directors, United Council for Neurologic Subspecialties neurocritical care fellowship program directors, and members of the Neurocritical Care Society. RESULTS: A total of 268 neurocritical care providers and neurology residents from 30 institutions responded. Overall, >90% supported NCC graduates independently interpreting and managing systemic and cerebral hemodynamic data, or performing brain death determination, neurovascular ultrasound, vascular access, and airway management. Over 75% endorsed that NCC graduates should independently interpret EEG and perform bronchoscopies. Fewer but substantial respondents supported graduates being independent performing intracranial bolt (45.8%), ventriculostomy (39.0%), tracheostomy (39.8%), or gastrostomy (19.1%) procedures. Trainees differed from physicians and program directors, respectively, by advocating independence in EEG interpretation (92.8%, 61.8%, and 65.3%) and PEG placement (29.3%, 9.1%, and 8.5%). CONCLUSIONS: Broad support exists across NCC role groups for wide-ranging NCC competencies including skills often performed by other neurology and non-neurology subspecialties. Variations highlight natural divergences in expectations among trainee, physician, and nurse role groups. These results establish expectations for core competencies within NCC and initiate dialogue across subspecialties about best practice standards for the spectrum of critically ill patients requiring neurologic care.

Preventing Early Bouncebacks to the Neurointensive Care Unit: A Retrospective Analysis and Quality Improvement Pilot.

BACKGROUND: Early unplanned readmissions of "bouncebacks" to intensive care units are a healthcare quality metric and result in higher mortality and greater cost. Few studies have examined bouncebacks to the neurointensive care unit (neuro-ICU), and we sought to design and implement a quality improvement pilot to reduce that rate. METHODS: First, we performed a retrospective chart review of 504 transfers to identify potential bounceback risk factors. Risk factors were assessed on the day of transfer by the transferring physician identifying patients as "high risk" or "low risk" for bounceback. "High-risk" patients underwent an enhanced transfer process emphasizing interdisciplinary communication and rapid assessment upon transfer during a 9-month pilot. RESULTS: Within the retrospective cohort, 34 of 504 (4.7%) transfers required higher levels of care within 48 h. Respiratory failure and sepsis/hypotension were the most common reasons for bounceback among this group. During the intervention, 8 of 225 (3.6%) transfers bounced back, all of who were labeled "high risk." Being "high risk" was associated with a risk of bounceback (OR not calculable, p = 0.02). Aspiration risk (OR 6.9; 95% CI 1.6-30, p = 0.010) and cardiac arrhythmia (OR 7.1; 95% CI 1.6-32, p = 0.01) were independent predictors of bounceback in multivariate analysis. Bounceback rates trended downward to 2.8% in the final phase (p for trend 0.09). Eighty-five percent of providers responded that the pilot should become standard of care. CONCLUSION: Patients at high risk for bounceback after transfer from the neuro-ICU can be identified using a simple tool. Early augmented multidisciplinary communication and care for high-risk patients may improve their management in the hospital.

Neurosurgical applications of viscoelastic hemostatic assays.

Patients taking antithrombotic agents are very common in neurosurgical practice. The perioperative management of these patients can be extremely challenging especially as newer agents, with poorly defined laboratory monitoring and reversal strategies, become more prevalent. This is especially true with emergent cases in which rapid reversal of anticoagulation is required and the patient's exact medical history is not available. With an aging patient population and the associated increase in diseases such as atrial fibrillation, it is expected that the use of these agents will continue to rise in coming years. Furthermore, thromboembolic complications such as deep venous thrombosis, pulmonary embolism, and myocardial infarction are common complications of major surgery. These trends, in conjunction with a growing understanding of the hemostatic process and its contribution to the pathophysiology of disease, stress the importance of the complete evaluation of a patient's hemostatic profile in guiding management decisions. Viscoelastic hemostatic assays (VHAs), such as thromboelastography and rotational thromboelastometry, are global assessments of coagulation that account for the cellular and plasma components of coagulation. This FDA-approved technology has been available for decades and has been widely used in cardiac surgery and liver transplantation. Although VHAs were cumbersome in the past, advances in software and design have made them more accurate, reliable, and accessible to the neurosurgeon. VHAs have demonstrated utility in guiding intraoperative blood product transfusion, identifying coagulopathy in trauma, and managing postoperative thromboprophylaxis. The first half of this review aims to evaluate and assess VHAs, while the latter half seeks to appraise the evidence supporting their use in neurosurgical populations.

The Effects of Red Blood Cell Transfusion on Functional Outcome after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The optimal red blood cell transfusion (RBCT) trigger for patients with aneurysmal subarachnoid hemorrhage (SAH) is unknown. In patients with cerebral vasospasm, anemia may increase susceptibility to ischemic injury; conversely, RBCT may worsen outcome given known deleterious effects. OBJECTIVE: To examine the association between RBCT, delayed cerebral ischemia (DCI), vasospasm, and outcome after SAH. METHODS: A total of 421 consecutive patients with SAH, admitted to a neurocritical care unit at a university-affiliated hospital and who underwent surgical occlusion of their ruptured aneurysm were retrospectively identified from a prospective observational database. Propensity score methods were used to reduce the bias associated with treatment selection. RESULTS: Two hundred and sixty-one patients (62.0%) received an RBCT. Angiographic vasospasm (odds ratio [OR] 1.6; 95% confidence interval [CI], 1.1-2.3; P = 0.025) but not severe angiographic spasm, DCI, or delayed infarction was associated with RBCT. A total of 283 patients (67.2%) experienced a favorable outcome, defined as good or moderately disabled on the Glasgow Outcome Scale; 47 (11.2%) were severely disabled or vegetative and 91 patients (21.6%) were dead at 6-month follow-up. Among patients who survived ≥2 days, RBCT was associated with unfavorable outcome (OR, 2.6; 95% CI, 1.6-4.1). Transfusion of ≥3 units of blood was associated with an increased incidence of unfavorable outcome. Propensity analysis to control for the probability of exposure to RBCT conditional on observed covariates measured before RBCT indicates that RBCT is associated with unfavorable outcome in the absence of DCI (OR, 2.17; 95% CI, 1.56-3.01; P < 0.0001) but not when DCI is present (OR, 0.82; 95% CI, 0.35-1.92; P = 0.65). CONCLUSIONS: Blood transfusions are associated with unfavorable outcome after SAH particularly when DCI is absent. Propensity analysis suggests that RBCT may be associated with poor outcome rather than being a marker of disease severity. However, when DCI is present, RBCT may help improve outcome.

Elevated Red Cell Distribution Width is Associated with Cerebral Infarction in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Elevated red blood cell distribution width (RDW) has been associated with thrombotic disorders including myocardial infarction, venous thromboembolism, and ischemic stroke, independent of other inflammatory and coagulation biomarkers. The purpose of this study was to determine whether elevated RDW is associated with cerebral infarction and poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In this retrospective single-center cohort of aSAH patients (October 2009-September 2014), elevated RDW was defined as a mean RDW >14.5 % during the first 14 days after aSAH. Outcomes included cerebral infarction (CI) by any mechanism and poor functional outcome, defined as discharge modified Rankin Scale (mRS) >4, indicating severe disability or death. RESULTS: Of 179 patients, 27 % had a high Hunt-Hess grade (IV-V), and 76 % were women. Twenty-four patients (13.4 %) underwent red blood cell (RBC) transfusion and compared to patients with normal RDW, patients with an elevated RDW were at greater odds of RBC transfusion (OR 2.56 [95 % CI, 1.07-6.11], p = 0.035). In univariate analysis, more patients with elevated RDW experienced CI (30.8 vs. 13.7 %, p = 0.017). In the multivariable model, elevated RDW was significantly associated with CI (OR 3.08 [95 % CI, 1.30-7.32], p = 0.011), independent of known confounders including but not limited to age, sex, race, high Hunt-Hess grade, and RBC transfusion. In multivariable analysis, RDW elevation was also associated with poor functional outcome (mRS > 4) at discharge (OR 2.59 [95 % CI, 1.04-629], p = 0.040). CONCLUSIONS: RDW elevation is associated with cerebral infarction and poor outcome after aSAH. Further evaluation of this association is warranted as it may shed light on mechanistic relations between anemia, inflammation, and thrombosis after aSAH.

Diagnosis and Management of Coagulopathy-Related Intracerebral Hemorrhage.

Coagulopathy, defined as impaired clot formation, is common in intensive care units (ICUs). Many physiological derangements lead to dysfunctional hemostasis in the ICU; most of these are acquired rather than congenital. Coagulopathies in the ICU are often related to systemic diseases, autoimmune dysfunction, acute infection, organ dysfunction, therapeutic medications, and/or other medical treatments. A significant complication of coagulopathy in the critically ill is major bleeding, defined as fatal hemorrhage, hemodynamic instability, transfusion requirement, or intracranial hematomas. Coagulopathy in the ICU often poses complex management dilemmas, especially when coagulopathy coexists with a thrombotic state. Coagulopathy associated with intracerebral hemorrhage (ICH) bears directly on neurologic prognosis and functional outcome. There is a paucity of high-quality evidence for the management of coagulopathies in neurocritical care; however, data derived from studies of patients with ICH may inform treatment decisions. This article focuses on acquired conditions such as pharmacological therapies, organ failure, and platelet dysfunction that are often associated with defective clot formation in the ICU that result in or exacerbate ICH.

Thromboelastography Parameter Predicts Outcome After Subarachnoid Hemorrhage: An Exploratory Analysis.

OBJECTIVE: Hypercoagulability after subarachnoid hemorrhage (SAH) is well described and may be platelet mediated. Thromboelastography (TEG) provides a global assessment of coagulation. We sought to determine whether the maximum amplitude (MA) parameter of TEG, a measure of platelet strength and function, is associated with outcome after SAH. METHODS: One hundred ten TEG analyses were performed for patients with moderate-to-severe SAH and compared with 6 healthy age- and sex-matched controls. TEG indices included MA, G value (G), alpha angle, and thrombus generation and were correlated to functional outcomes and laboratory tests including complete blood count, erythrocyte sedimentation rate, high sensitivity C-reactive protein, fibrinogen, and d-dimer, obtained on post-bleed days (PBDs) 1, 3, 5, 7, and 10. RESULTS: MA was significantly elevated compared with controls on PBD 3 (70.0 mm ± 4.5 mm vs. 64.1 mm ± 6.5 mm; P = 0.02), PBD 5 (72.6 mm ± 5.3 mm vs. 64.1 mm ± 6.5 mm; P = 0.003), PBD 7 (73.0 mm ± 5.4 mm vs. 64.1 mm ± 6.5 mm; P = 0.003), and PBD 10 (73.4 mm ± 6.0 mm vs. 64.1 mm ± 6.5 mm; P = 0.005). G was significantly elevated compared with controls on PBD 3 (P = 0.03), PBD 5 (P = 0.01), PBD 7 (P = 0.01), and PBD 10 (P = 0.02). The only biomarker associated with poor outcome was CRP. Multivariate logistic regression demonstrated an association between elevated MA and outcome (odds ratio 39.1, P = 0.006) independent of CRP, age, Hunt Hess grade, and transfusion. CONCLUSIONS: TEG indices are associated with poor outcome after SAH and may identify a platelet-mediated hypercoagulable state. The association between MA and outcome was stronger than that between traditional biomarkers and was independent of age and Hunt Hess grade.

Sleep Features on Continuous Electroencephalography Predict Rehabilitation Outcomes After Severe Traumatic Brain Injury.

OBJECTIVE: Sleep characteristics detected by electroencephalography (EEG) may be predictive of neurological recovery and rehabilitation outcomes after traumatic brain injury (TBI). We sought to determine whether sleep features were associated with greater access to rehabilitation therapies and better functional outcomes after severe TBI. METHODS: We retrospectively reviewed records of patients admitted with severe TBI who underwent 24 or more hours of continuous EEG (cEEG) monitoring within 14 days of injury for sleep elements and ictal activity. Patient outcomes included discharge disposition and modified Rankin Scale (mRS). RESULTS: A total of 64 patients underwent cEEG monitoring for a mean of 50.6 hours. Status epilepticus or electrographic seizures detected by cEEG were associated with poor outcomes (death or discharge to skilled nursing facility). Sleep characteristics were present in 19 (30%) and associated with better outcome (89% discharged to home/acute rehabilitation; P = .0002). Lack of sleep elements on cEEG correlated with a poor outcome or mRS > 4 at hospital discharge (P = .012). Of those patients who were transferred to skilled nursing/acute rehabilitation, sleep architecture on cEEG associated with a shorter inpatient hospital stay (20 days vs 27 days) and earlier participation in therapy (9.8 days vs 13.2 days postinjury). Multivariable analyses indicated that sleep features on cEEG predicted functional outcomes independent of admission Glasgow Coma Scale and ictal-interictal activity. CONCLUSION: The presence of sleep features in the acute period after TBI indicates earlier participation in rehabilitative therapies and a better functional recovery. By contrast, status epilepticus, other ictal activity, or absent sleep architecture may portend a worse prognosis. Whether sleep elements detected by EEG predict long-term prognosis remains to be determined.

Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage: A Statement for Healthcare Professionals from the Neurocritical Care Society and Society of Critical Care Medicine.

BACKGROUND: The use of antithrombotic agents, including anticoagulants, antiplatelet agents, and thrombolytics has increased over the last decade and is expected to continue to rise. Although antithrombotic-associated intracranial hemorrhage can be devastating, rapid reversal of coagulopathy may help limit hematoma expansion and improve outcomes. METHODS: The Neurocritical Care Society, in conjunction with the Society of Critical Care Medicine, organized an international, multi-institutional committee with expertise in neurocritical care, neurology, neurosurgery, stroke, hematology, hemato-pathology, emergency medicine, pharmacy, nursing, and guideline development to evaluate the literature and develop an evidence-based practice guideline. Formalized literature searches were conducted, and studies meeting the criteria established by the committee were evaluated. RESULTS: Utilizing the GRADE methodology, the committee developed recommendations for reversal of vitamin K antagonists, direct factor Xa antagonists, direct thrombin inhibitors, unfractionated heparin, low-molecular weight heparin, heparinoids, pentasaccharides, thrombolytics, and antiplatelet agents in the setting of intracranial hemorrhage. CONCLUSIONS: This guideline provides timely, evidence-based reversal strategies to assist practitioners in the care of patients with antithrombotic-associated intracranial hemorrhage.