Code ICH: A Call to Action.

Intracerebral hemorrhage is the most serious type of stroke, leading to high rates of severe disability and mortality. Hematoma expansion is an independent predictor of poor functional outcome and is a compelling target for intervention. For decades, randomized trials aimed at decreasing hematoma expansion through single interventions have failed to meet their primary outcomes of statistically significant improvement in neurological outcomes. A wide range of evidence suggests that ultra-early bundled care, with multiple simultaneous interventions in the acute phase, offers the best hope of limiting hematoma expansion and improving functional recovery. Patients with intracerebral hemorrhage who fail to receive early aggressive care have worse outcomes, suggesting that an important treatment opportunity exists. This consensus statement puts forth a call to action to establish a protocol for Code ICH, similar to current strategies used for the management of acute ischemic stroke, through which early intervention, bundled care, and time-based metrics have substantially improved neurological outcomes. Based on current evidence, we advocate for the widespread adoption of an early bundle of care for patients with intracerebral hemorrhage focused on time-based metrics for blood pressure control and emergency reversal of anticoagulation, with the goal of optimizing the benefit of these already widely used interventions. We hope Code ICH will endure as a structural platform for continued innovation, standardization of best practices, and ongoing quality improvement for years to come.

Multicenter Comparison of the Safety and Efficacy of Clopidogrel Versus Ticagrelor for Neuroendovascular Stents.

BACKGROUND: Dual antiplatelet therapy (DAPT) is commonly employed for neuroendovascular stenting due to the significant risk of thromboembolism. Clopidogrel and aspirin are most often selected as initial DAPTs; however, there is limited literature available to support guidance of DAPT in this setting. The objective of this study was to evaluate safety and efficacy in patients whose final regimen included either DAPT with aspirin and clopidogrel (DAPT-C) or DAPT with aspirin and ticagrelor (DAPT-T). METHODS: This was a multicenter, retrospective cohort of patients who underwent neuroendovascular stenting and received DAPT between July 1, 2017, and October 31, 2020. Study participants were allocated into groups based on discharge DAPT regimen. The primary outcome was incidence of stent thrombosis at 3-6 months on DAPT-C versus DAPT-T, as defined by the presence of thrombus on imaging or new onset stroke. Secondary outcomes included major and minor bleeding and death within 3-6 months after the procedure. RESULTS: Five hundred and seventy patients were screened across 12 sites. Of those, 486 were included (DAPT-C n = 360, DAPT-T n = 126). There was no difference in the primary outcome of stent thrombosis between the DAPT-C and DAPT-T groups (8% vs. 8%, p = 0.97) and no difference in any of the secondary safety outcomes. CONCLUSIONS: Using DAPT-C or DAPT-T regimens in a broad population of neuroendovascular stenting procedures appears to have similar safety and efficacy profiles. Further prospective evaluation is warranted to streamline the practice of DAPT selection and monitoring to determine the impact on clinical outcomes.

Positive emotion in posttraumatic stress disorder: A global or context-specific problem?

Problems with positive emotion are an important component of posttraumatic stress disorder (PTSD), with competing perspectives as to why. The global model suggests that people with PTSD experience a relatively permanent shift in their capacity for positive emotion regardless of context, whereas the context-specific model posits access to the full repertoire of positive emotion that only becomes reduced during exposure to trauma reminders. We tested the global versus context-specific models using ecological momentary assessment (EMA). Trauma-exposed adult community members (N = 80) with (n = 39) and without diagnosed PTSD completed 3 days of EMA (n = 2,158 observations). Participants with PTSD reported lower average momentary levels of positive emotion, B = -0.947, 95% CI [-1.35, -0.54], p < .001, and positive situations, B = -0.607, 95% CI [-1.16, -0.05], p = .032, and more thinking about trauma reminders, B = 0.360, 95% CI [0.21, 0.51], p < .001. There was no between-group difference in positive emotion reactivity (degree of positive emotion derived from positive situations), B = 0.03, 95% CI [-0.09, 0.14], p = .635. Increased thinking about trauma reminders predicted lower momentary levels of positive emotion, B = -0.55, 95% CI [-0.83, -0.26], p < .001, but not reactivity, B = 0.02, 95% CI [-0.35, 0.40], p = .906, irrespective of PTSD status. Findings supported the global model and were inconsistent with the context-specific model. This study helps clarify positive emotional functioning in trauma-exposed adults and highlights future directions to better understand problems with positive emotion in PTSD.

Effects of trauma-focused rumination among trauma-exposed individuals with and without posttraumatic stress disorder: An experiment.

Rumination, or thinking repetitively about one's distress, is a risk factor for posttraumatic stress disorder (PTSD). Current theories suggest that rumination contributes to PTSD symptoms directly, by increasing negative reactions to trauma cues (i.e., symptom exacerbation), or represents a form of cognitive avoidance, if verbal ruminations are less distressing than trauma imagery. The goal of this study was to test the symptom exacerbation and cognitive avoidance accounts of trauma-focused rumination. We recruited 135 trauma-exposed participants (n = 60 diagnosed with PTSD) and randomly assigned them to ruminate about their trauma, distract themselves, or engage in trauma imagery. For individuals with and without PTSD, rumination led to larger increases in subjective distress (i.e., negative affect, fear, sadness, subjective arousal, valence) than distraction, ηp 2 s = .04-.13, but there were no differences between rumination and imagery ηp 2 s = .001-.02. We found no evidence that rumination or imagery elicited physiological arousal, ds = 0.01-0.19, but did find that distraction reduced general physiological arousal, as measured by heart rate, relative to baseline, d = 0.84, which may be due to increases in parasympathetic nervous system activity (i.e., respiratory sinus arrhythmia), d = 0.33. These findings offer no support for the avoidant function of rumination in PTSD. Instead, the findings were consistent with symptom exacerbation, indicating that rumination leads directly to emotional reactivity to trauma reminders and may be a fruitful target in PTSD intervention.

Posttraumatic stress disorder-related anhedonia as a predictor of psychosocial functional impairment among United States veterans.

Prior research suggests that anhedonia symptoms related to posttraumatic stress disorder (PTSD; i.e., diminished interest, detachment from others, and difficulty experiencing positive emotions) are consistently associated with a higher degree of impairment in psychosocial functioning beyond that associated with other PTSD symptoms. Unfortunately, much of this research has used cross-sectional study designs; relied upon outdated DSM diagnostic criteria; and failed to control for potentially confounding variables, such as the presence of co-occurring depression. This study used data from Waves 2 and 4 (n = 1,649) of the Veterans' After-Discharge Longitudinal Registry (Project VALOR), a longitudinal dataset of U.S. Army and Marine veterans. As measured using the Inventory of Psychosocial Functioning, Wave 4 psychosocial functioning was regressed on seven PTSD symptom factors at Wave 2 (i.e., intrusions, avoidance, negative affect, anhedonia, externalizing behaviors, anxious arousal, and dysphoric arousal) and potential Wave 2 confounds. The Anhedonia factor, ß = .123, most strongly predicted later psychosocial functional impairment beyond the impact of other PTSD symptom factors, ßs = -.076-.046. Clinical implications of these findings are also discussed.

Review of Target-Specific Anticoagulation Reversal Agents.

Bleeding related to direct oral anticoagulants accounts for nearly half of emergency department visits annually and until recently there were no reversal antidotes available. As there continues to be a shift in prescribing practices away from warfarin, it is essential to have these reversal agents readily available for the treatment of life-threatening bleeds associated with these anticoagulants. In addition, for agents that continue to lack a targeted reversal agent (eg, low-molecular-weight heparin, antiplatelets, and new antithrombotics), it is imperative that research continues to evaluate improved reversal strategies. This review focuses on target-specific anticoagulation reversal agents currently available in the United States (protamine, idarucizumab, and andexanet alfa) and summarizes agents that are in the pipeline for these anticoagulants and antiplatelets.

Management of warfarin-associated intracerebral hemorrhage before and after implementation of an order set and prospective pharmacist order verification.

Management of warfarin-associated intracerebral hemorrhage (ICH) necessitates rapid reversal of anticoagulation. Guideline-based management of warfarin-associated ICH includes timely administration of prothrombin complex concentrate (PCC) and intravenous (IV) vitamin K. In 2017, our hospital implemented an order set for warfarin reversal to facilitate computerized provider order entry (CPOE), and the pharmacy department began prospective verification and dispensing of all PCC orders for anticoagulant reversal. We sought to compare the proportion of patients who received timely, guideline-based therapy for warfarin-associated ICH before and after these changes. We conducted a single-center, retrospective cohort study of all warfarin-associated ICH patients who had an order for PCC. A total of 66 patients were included; 32 patients (pre-intervention cohort) were evaluated in the 2 year period prior to the process improvement changes, while 34 patients (post-intervention cohort) were evaluated in the 2 year period following these changes. Baseline characteristics were similar between groups. The proportion of patients receiving timely guideline-based therapy was significantly higher in the post-intervention cohort compared to the pre-intervention cohort (76.5% vs 34.4%, p < 0.001), primarily driven by increased ordering of vitamin K 10 mg IV in conjunction with PCC in the post-intervention cohort. Our results indicate that implementation of an order set to assist with CPOE, in addition to prospective pharmacist verification of PCC orders, leads to increased adherence to guideline-based management of warfarin-associated ICH.

Management of tandem occlusions in patients who receive rtPA.

BACKGROUND: Tandem occlusions exist in 17-32% of large vessel occlusion (LVO) strokes. A significant concern is bleeding when carotid stenting is performed in tandem with thrombectomy due the administration of antiplatelet agents such as glycoprotein IIb/IIIa inhibitors (GP2b3aI) after receiving rtPA, but data are limited in this setting. METHODS: A mutlicenter, retrospective chart review was conducted at two comprehensive stroke centers to assess the safety and efficacy of using GP2b3aI to facilitate carotid stent placement simultaneously with endovascular thrombectomy in patients who have received rtPA. RESULTS: Overall, 32 patients were included in this study, with average age of 66.3 ± 10.4 years and predominantly male (87.5%). The cause of stroke was mostly large artery atherosclerosis (59.4%) and the thrombectomy target vessels were typically first- or second segment middle cerebral artery (37.5% and 31.3%). Time from symptom onset to rtPA bolus was 1.8 h [interquartile range (IQR) 1.5-2.7], rtPA bolus to first pass was 2 h [IQR 1.5-3.1], rtPA bolus to GP2b3aI bolus was 2 h [IQR 1.6-3.5], and rtPA bolus to aspirin and clopidogrel administration was 4.3 h [IQR 2.6-8.9] and 6.6 h [IQR 4.5-11.6] respectively. No patients had acute in-stent thrombosis or post-op bleeding from the access site. Two patients (6.3%) had significant hemorrhagic conversion. CONCLUSION: The use of GP2b3aI in the setting of tandem occlusions that required emergent stent placement post-rtPA appears safe and effective. Given the small sample size, these findings should be interpreted cautiously, and need to be confirmed in a larger patient population.

Facilitators and Barriers to Nursing Implementation of Continuous Glucose Monitoring (CGM) in Critically Ill Patients With COVID-19.

OBJECTIVE: We describe our implementation of a continuous glucose monitoring (CGM) guideline to support intravenous insulin administration and reduce point of care (POC) glucose monitoring frequency in the coronavirus disease 2019 medical intensive care unit (MICU) and evaluate nurses' experience with implementation of CGM and hybrid POC + CGM protocol using the Promoting Action on Research in Health Services framework. METHODS: A multidisciplinary team created a guideline providing criteria for establishing initial sensor-meter agreement within each individual patient followed by hybrid use of CGM and POC. POC measures were obtained hourly during initial validation, then every 6 hours. We conducted a focus group among MICU nurses to evaluate initial implementation efforts with content areas focused on initial assessment of evidence, context, and facilitation to identify barriers and facilitators. The focus group was analyzed using a qualitative descriptive approach. RESULTS: The protocol was integrated through a rapid cycle review process and ultimately disseminated nationally. The Diabetes Consult Service performed device set-up and nurses received just-in-time training. The majority of barriers centered on contextual factors, including limitations of the physical environment, complex device set-up, hospital firewalls, need for training, and CGM documentation. Nurses' perceived device accuracy and utility were exceptionally high. Solutions were devised to maximize facilitation and sustainability for nurses while maintaining patient safety. CONCLUSION: Outpatient CGM systems can be implemented in the MICU using a hybrid protocol implementation science approach. These efforts hold tremendous potential to reduce healthcare worker exposure while maintaining glucose control during the COVID-19 pandemic.

Stress-Related Gastrointestinal Bleeding in Patients with Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Observational Study.

BACKGROUND/OBJECTIVE: Stress-related mucosal bleeding (SRMB) occurs in approximately 2-4% of critically ill patients. Patients with aneurysmal subarachnoid hemorrhage (aSAH) have a (diffuse) space-occupying lesion, are critically ill, often require mechanical ventilation, and frequently receive anticoagulation or antiplatelet therapy after aneurysm embolization, all of which may be risk factors for SRMB. However, no studies have evaluated SRMB in patients with aSAH. Aims of the study were to determine the incidence of SRMB in aSAH patients, evaluate the effect of acid suppression on SRMB, and identify specific risk factors for SRMB. METHODS: This was a multicenter, retrospective, observational study conducted across 17 centers. Each center reviewed up to 50 of the most recent cases of aSAH. Patients with length of stay (LOS) < 48 h or active GI bleeding on admission were excluded. Variables related to demographics, aSAH severity, gastrointestinal (GI) bleeding, provision of SRMB prophylaxis, adverse events, intensive care unit (ICU), and hospital LOS were collected for the first 21 days of admission or until hospital discharge, whichever came first. Descriptive statistics were used to analyze the data. A multivariate logistic regression modeling was utilized to examine the relationship between specific risk factors and the incidence of clinically important GI bleeding in patients with aSAH. RESULTS: A total of 627 patients were included. The overall incidence of clinically important GI bleeding was 4.9%. Of the patients with clinically important GI bleeding, 19 (61%) received pharmacologic prophylaxis prior to evidence of GI bleeding, while 12 (39%) were not on pharmacologic prophylaxis at the onset of GI bleeding. Patients who received an acid suppressant agent were less likely to experience GI bleeding than patients who did not receive pharmacologic prophylaxis prior to evidence of bleeding (OR 0.39, 95% CI 0.18-0.83). The multivariate regression analysis identified any instance of elevated intracranial pressure, creatinine clearance < 60 ml/min and the incidence of cerebral vasospasm as specific risk factors associated with GI bleeding. Cerebral vasospasm has not previously been described as a risk for GI bleeding (OR 2.5 95% CI 1.09-5.79). CONCLUSIONS: Clinically important GI bleeding occurred in 4.9% of patients with aSAH, similar to the general critical care population. Risk factors associated with GI bleeding were prolonged mechanical ventilation (> 48 h), creatinine clearance < 60 ml/min, presence of coagulopathy, elevation of intracranial pressure, and cerebral vasospasm. Further prospective research is needed to confirm this observation within this patient population.

Pharmacy-Based Nursing Education Utilizing a Social Media Platform.

Social media has changed the way individuals communicate and recently multiple articles have been published highlighting the utilization of social media for education. To our knowledge, cross-discipline education utilizing these platforms has not been evaluated. The purpose of this study was to implement a pharmacist-led, social media-based nursing education program and evaluate the perceived value. A curriculum of pharmacy-related issues was developed and topics were posted to the neurocritical care unit (NCCU) Facebook group or emailed to non-Facebook users weekly. A pre- and posteducation survey was sent out evaluating the program's effectiveness. Thirty-seven nurses were members of the NCCU Facebook group and 33 received the education via email. A total of 29% and 19% of nurses completed the pre- and posteducation survey, respectively. Of those who completed the survey, 36% received education via Facebook. As compared with the preeducation survey, there were no statistically significant differences in nursing performance on fact-based questions (P value > .05 on all assessment questions); however, 100% of respondents wanted to continue this education delivery. Utilizing social media as a means of cross-discipline education was well-received; however, the solitary utilization should be used cautiously, as performance did not improve on assessment questions.

Assessment of Acute Kidney Injury in Neurologically Injured Patients Receiving Hypertonic Sodium Chloride: Does Chloride Load Matter?

Background: Increasing evidence suggests that large-volume infusions of 0.9% sodium chloride (NaCl) for resuscitation are associated with hyperchloremic metabolic acidosis, renal vasoconstriction, and increased risk of acute kidney injury (AKI). Patients with neurological injury may require hypertonic NaCl for therapeutic hypernatremia, treatment of cerebral salt wasting, hyponatremia, or elevated intracranial pressure. Consequently, this increased exposure to chloride may result in an increased risk for development of AKI. Objective: The primary aim of this study was to describe the risk for development of AKI in neurologically injured patients receiving large volumes of intravenous hypertonic NaCl. Methods: This single-center, retrospective study looked at neurologically injured patients who received hypertonic NaCl and sodium acetate. Data were collected to assess renal function, hyperchloremia, and acidemia. Receiver operating characteristic (ROC) curve analysis was used to determine the predictive association between the amount of daily and overall chloride exposure and development of AKI. Results: A total of 301 patients were screened, and of those, 142 were included. Of the 142 patients included, 13% developed AKI, and 38% developed hyperchloremia. Additionally, 32% of patients were switched from NaCl to sodium acetate after an average of 3.4 ± 1.5 days of NaCl therapy. The ROC curve demonstrated that if patients received greater than 2055 mEq of chloride over 7 days, they were more likely to develop AKI (sensitivity 72%, specificity 70%; P = 0.002; area under the curve = 0.7). Conclusion and Relevance: Neurologically injured patients receiving hypertonic sodium therapy with a high chloride load are at risk of developing hyperchloremia and AKI.

Pharmacologic Management of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is responsible for 5% to 10% of all strokes in the United States annually and is a neurologic emergency with considerable morbidity and mortality. A common complication of aSAH is cerebral vasospasm (CVS) or narrowing of the cerebral arteries. While nearly 70% of aSAH patients will develop CVS, approximately 30% of those patients will go on to develop delayed cerebral ischemia, defined as symptomatic vasospasm or cerebral infarction demonstrated on imaging. While the pathophysiology of CVS is unclear, the prevention and treatment of this complication are a focus of ongoing research. Despite continued efforts, only one medication, nimodipine, is Food and Drug Administration approved for the improvement of neurologic outcomes by reducing the incidence and severity of ischemic deficits in patients with CVS during aSAH. This review provides nurse practitioners and the bedside nursing staff with a summary of the available literature on the pharmacologic management of CVS. It focuses on oral, intravenous, intra-arterial, and intraventricular medications available in the United States that may be utilized in the management of CVS.

Acute Thrombocytopenia After Tissue Plasminogen Activator for Stroke.

We present what may be the first case report of acute thrombocytopenia after tissue plasminogen activator (tPA) in the setting of stroke. Early fibrinogen degradation coagulopathy (EFDC) after tPA has been described in the past and acute thrombocytopenia may fall into this spectrum. Further studies are needed to evaluate the bleeding and mortality risk associated with thrombocytopenia after tPA.

Adjusted versus actual body weight dosing of 4-factor prothrombin complex concentrate in obese patients with warfarin-associated major bleeding.

The package insert of 4-factor prothrombin complex concentrate (4F-PCC) contains specific dosing recommendations stating to determine the patients dose based on their INR and weight, capping the weight at 100 kg. However, the mean body mass index (BMI) in the 4F-PCC U.S. approval study was 27 kg/m2, and there is a lack of literature identifying the ideal dosing strategy in obesity. We conducted a retrospective analysis of obese patients (BMI ≥ 30 kg/m2) who received 4F-PCC for warfarin associated emergent bleeding reversal. Treatment groups were those that received 4F-PCC on adjusted body weight (AdjBW) and those on actual body weight (ActBW). The primary outcome was the percent of patients achieving coagulopathy reversal, defined as a post-treatment INR < 1.4 for neurologic indications and < 1.5 for all others. A total of 78 obese patients were included (28 AdjBW and 50 ActBW). Baseline INR (3.1 vs. 2.8; p = 0.052) and BMI (33.6 vs. 33.6 kg/m2) were similar between groups. Achievement of goal INR was significantly lower in the AdjBW group (36% vs. 68%; p = 0.006). A majority of patients had intracranial hemorrhage (32% vs. 54%; p = 0.06), and the median dose of 4F-PCC was lower in the AdjBW group (2120 vs. 2500 units; p = 0.02). Dosing 4F-PCC using adjusted body weight in obese patients resulted in a significantly lower rate of coagulopathy reversal. ActBW should be used to dose 4F-PCC in obese patients when the 100 kg dose cap is utilized per the package insert recommendations.

Acute Management of Hypertension Following Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is responsible for approximately 15% of strokes annually in the United States, with nearly 1 in 3 of these patients dying without ever leaving the hospital. Because this disproportionate mortality risk has been stagnant for nearly 3 decades, a main area of research has been focused on the optimal strategies to reduce mortality and improve functional outcomes. The acute hypertensive response following ICH has been shown to facilitate ICH expansion and is a strong predictor of mortality. Rapidly reducing blood pressure was once thought to induce cerebral ischemia, though has been found to be safe in certain patient populations. Clinicians must work quickly to determine whether specific patient populations may benefit from acute lowering of systolic blood pressure (SBP) following ICH. This review provides nurses with a summary of the available literature on blood pressure control following ICH. It focuses on intravenous and oral antihypertensive medications available in the United States that may be utilized to acutely lower SBP, as well as medications outside of the antihypertensive class used during the acute setting that may reduce SBP.

Moral injury in U.S. combat veterans: Results from the national health and resilience in veterans study.

BACKGROUND: Combat exposure is associated with increased risk of mental disorders and suicidality. Moral injury, or persistent effects of perpetrating or witnessing acts that violate one's moral code, may contribute to mental health problems following military service. The pervasiveness of potentially morally injurious events (PMIEs) among U.S. combat veterans, and what factors are associated with PMIEs in this population remains unknown. METHODS: Data were analyzed from the National Health and Resilience in Veterans Study (NHRVS), a contemporary and nationally representative survey of a population-based sample of U.S. veterans, including 564 combat veterans, collected September-October 2013. Types of PMIEs (transgressions by self, transgressions by others, and betrayal) were assessed using the Moral Injury Events Scale. Psychiatric and functional outcomes were assessed using established measures. RESULTS: A total of 10.8% of combat veterans acknowledged transgressions by self, 25.5% endorsed transgressions by others, and 25.5% endorsed betrayal. PMIEs were moderately positively associated with combat severity (ß = .23, P < .001) and negatively associated with white race, college education, and higher income (ßs = .11-.16, Ps < .05). Transgressions by self were associated with current mental disorders (OR = 1.65, P < .001) and suicidal ideation (OR = 1.67, P < .001); betrayal was associated with postdeployment suicide attempts (OR = 1.99, P < .05), even after conservative adjustment for covariates, including combat severity. CONCLUSIONS: A significant minority of U.S combat veterans report PMIEs related to their military service. PMIEs are associated with risk for mental disorders and suicidality, even after adjustment for sociodemographic variables, trauma and combat exposure histories, and past psychiatric disorders.

Augmented Renal Clearance in Patients with Subarachnoid Hemorrhage.

BACKGROUND: Patients with subarachnoid hemorrhage (SAH) typically exhibit hyperdynamic cardiovascular hemodynamics, which may lead to increased medication clearance. The aims of this study were to evaluate the actual creatinine clearance (CrClA) in an aneurysmal SAH population and the effect of the development of cerebral vasospasm (CV) along with its treatment to better understand if this population exhibits augmented renal clearance (ARC). METHODS: This was a prospective, single-center study in a neurosciences ICU at a university hospital. A total of 20 patients were consented and provided a 24-h urine sample to measure the CrClA. If patients experienced CV, a 24-h urine collection was repeated during vasospasm treatment. CrClA was measured using a modified Jaffe assay. RESULTS: Among the 20 patients enrolled, the mean SAH CrClA was 325.93 ± 135.20 ml/min 1.73 m(2) and this differed significantly from the SAH estimated creatinine clearance (CrClE) 144.93 ± 42.82 ml/min 1.73 m(2) (p < 0.001). Four patients developed CV; the mean CV CrClA was 558.43 ± 356.12 ml/min 1.73 m(2) and there was no significant difference when compared to those patients' mean SAH CrClA (246.91 ± 84.14 ml/min 1.73 m(2), p = 0.16). CONCLUSIONS: ARC was present in 100 % of the patients with recent SAH enrolled. Although ARC remained present in the patients who experienced CV, their creatinine clearance was not significantly further augmented. Further work is needed to clarify the impact of such clearances on renally excreted medications and how the development and treatment of CV further augment these findings.