Major Bleeding Postadministration of Tenecteplase Versus Alteplase in Acute Ischemic Stroke.

BACKGROUND: Tenecteplase is a genetically engineered fibrinolytic with growing interest in the treatment of acute ischemic stroke. Compared to alteplase, tenecteplase is effective for neurologic improvement following ischemic stroke in patients with large vessel occlusions who are eligible for thrombectomy and for mild ischemic strokes with National Institutes of Health Stroke Scale of 0 to 5. OBJECTIVE: The purpose of this study is to determine if safety outcomes are different in patients receiving tenecteplase and alteplase for acute ischemic stroke. METHODS: This retrospective cohort reviewed all patients who received alteplase or tenecteplase from January 2019 to December 2020. Patients admitted before April 28, 2020, received alteplase intravenous bolus over 1 minute followed by an infusion over 1 hour, for a total of 0.9 mg/kg. Patients admitted after this date received tenecteplase 0.25 mg/kg as an intravenous bolus over 5 to 10 seconds. Any patient transferring from an outside facility was excluded. The primary outcome was major bleeding. RESULTS: There was no significant difference in major bleeding between alteplase and tenecteplase (40 [18%] vs 21 [18.1%], P = 0.985). There was no significant difference in all-cause inpatient mortality for alteplase versus tenecteplase (10 [5%] vs 5 [4%], P = 0.934) or in adverse events between the groups (22 [9%] vs 14 [12%], P = 0.541) for alteplase and tenecteplase, respectively. CONCLUSIONS AND RELEVANCE: Tenecteplase had similar rates of major bleeding versus alteplase and may be a reasonable alternative in the treatment of acute ischemic stroke.

Activated Prothrombin Complex Concentrates for the Treatment of Factor Xa Inhibitor-Associated Spontaneous Intracerebral Hemorrhage.

Background: Anticoagulant-associated intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality. Despite approval of a specific reversal agent for factor Xa inhibitors, there is still much interest in nonspecific reversal agents, such as activated prothrombin complex concentrates (aPCCs). Objective: The objective of this study was to describe ICH expansion in a cohort of patients with factor Xa inhibitor-associated ICH who were treated with aPCC. Methods: This was a retrospective cohort study conducted at an academic medical center designated as a comprehensive stroke center. Consecutive patients admitted for ICH who reported use of apixaban or rivaroxaban prior to admission were considered for inclusion in the study. Patients were treated with 25 to 50 units/kg of aPCC. Intracerebral hemorrhage volume was measured before administration of aPCC and then again within 36 hours of aPCC administration. Results: A total of 40 patients were included in the final analysis. Overall, the cohort was predominantly male (24 [60%]), white (27 [67.5%]), and the mean age was 75.3 ± 10.5 years. Most patients reported taking apixaban prior to admission (31 [77.5%]) and a large proportion were also taking aspirin (13 [32.5%]). The mean change in ICH volume was 1.12 ± 6.03 mL (P = 0.2475). Conclusions and Relevance: There was a nonsignificant change in mean ICH volume and no reported cases of thromboembolism. Due to the relatively high proportion of patients with significant hematoma expansion, more studies are needed on which patient population would best benefit from treatment with aPCC.

Concise Definitive Review for Reinitiation of Antidepressants, Antipsychotics, and Gabapentinoids in ICU Patients.

OBJECTIVE: Concise definitive review of the reinitiation of prior-to-admission neuropsychiatric medications (NPMs) in ICU patients. DATA SOURCES: Available literature on PubMed and MEDLINE databases. STUDY SELECTION: Available clinical trials and observational studies addressing the reinitiation of select NPMs (antidepressants, antipsychotics, and gabapentinoids) on various outcomes were included. DATA EXTRACTION: Eligible studies were identified by authors, and recommendations were summarized. DATA SYNTHESIS: Agitation and delirium are recognized as common complications of patients in the ICU. While there is literature that suggests patients can acutely withdraw from opioids, less data are known about withdrawal from NPM such as antidepressants, antipsychotics, and gabapentinoids. However, there is some literature that suggests reinitiating some NPMs may lead to reductions in agitation, delirium, and hospital and ICU length of stay. CONCLUSIONS: Additional larger studies are needed to evaluate the safety and efficacy of reinitiation of select prior-to-admission NPM to prevent agitation and delirium in ICU patients. Multiple factors for NPM reinitiation should be considered, such as reason for admission, organ dysfunction, available route of administration to provide prior-to-admission NPM, concomitant additional medications for agitation and delirium, and safety of these medications for patients in the ICU.

Impact of Pharmacists to Improve Patient Care in the Critically Ill: A Large Multicenter Analysis Using Meaningful Metrics With the Medication Regimen Complexity-ICU (MRC-ICU) Score.

OBJECTIVES: Despite the established role of the critical care pharmacist on the ICU multiprofessional team, critical care pharmacist workloads are likely not optimized in the ICU. Medication regimen complexity (as measured by the Medication Regimen Complexity-ICU [MRC-ICU] scoring tool) has been proposed as a potential metric to optimize critical care pharmacist workload but has lacked robust external validation. The purpose of this study was to test the hypothesis that MRC-ICU is related to both patient outcomes and pharmacist interventions in a diverse ICU population. DESIGN: This was a multicenter, observational cohort study. SETTING: Twenty-eight ICUs in the United States. PATIENTS: Adult ICU patients. INTERVENTIONS: Critical care pharmacist interventions (quantity and type) on the medication regimens of critically ill patients over a 4-week period were prospectively captured. MRC-ICU and patient outcomes (i.e., mortality and length of stay [LOS]) were recorded retrospectively. MEASUREMENTS AND MAIN RESULTS: A total of 3,908 patients at 28 centers were included. Following analysis of variance, MRC-ICU was significantly associated with mortality (odds ratio, 1.09; 95% CI, 1.08-1.11; p < 0.01), ICU LOS (ß coefficient, 0.41; 95% CI, 00.37-0.45; p < 0.01), total pharmacist interventions (ß coefficient, 0.07; 95% CI, 0.04-0.09; p < 0.01), and a composite intensity score of pharmacist interventions (ß coefficient, 0.19; 95% CI, 0.11-0.28; p < 0.01). In multivariable regression analysis, increased patient: pharmacist ratio (indicating more patients per clinician) was significantly associated with increased ICU LOS (ß coefficient, 0.02; 0.00-0.04; p = 0.02) and reduced quantity (ß coefficient, -0.03; 95% CI, -0.04 to -0.02; p < 0.01) and intensity of interventions (ß coefficient, -0.05; 95% CI, -0.09 to -0.01). CONCLUSIONS: Increased medication regimen complexity, defined by the MRC-ICU, is associated with increased mortality, LOS, intervention quantity, and intervention intensity. Further, these results suggest that increased pharmacist workload is associated with decreased care provided and worsened patient outcomes, which warrants further exploration into staffing models and patient outcomes.

Impact of Factor Xa Inhibitor Reversal with Prothrombin Complex Concentrate in Patients with Traumatic Brain Injuries.

BACKGROUND: Anticoagulant use prior to trauma has been associated with increased incidence of traumatic brain injury (TBI), intracranial hemorrhage (ICH) progression, and mortality. Prothrombin complex concentrates (PCCs) are commonly used as off-label treatments for factor Xa inhibitor-associated life-threatening hemorrhage. At this time, there is no consensus regarding appropriate indication, target dose, or outcomes of PCC administration in patients presenting with traumatic ICH. This study seeks to evaluate the impact of reversal with PCC on hemorrhage progression and outcomes in patients with TBI on preinjury factor Xa inhibitors. METHODS: This single-center retrospective cohort study included patients ≥ 18 years presenting with an acute TBI of any severity on apixaban or rivaroxaban from September 1, 2016, to September 1, 2019. Patients were grouped on the basis of receipt of PCCs for reversal (i.e., reversal or no reversal). Exclusion criteria included spontaneous ICH or known coagulopathy. Propensity score matching was conducted with the following variables: age, Abbreviated Injury Scale (head) score, and Charlson Comorbidity Index score. The primary outcome was hemorrhage stability within 48 h. Secondary outcomes included degree of hemorrhage progression, in-hospital mortality, discharge disposition, and incidence of thromboembolic events. RESULTS: Of the 115 patients meeting inclusion criteria, 84 were included in the propensity score matched data set. Baseline characteristics, comorbidities, and TBI severity were similar. The majority of patients in the reversal group (35 [83.3%]) and the no reversal (NR) group (40 [95.2%]) experienced a mild TBI (admission Glasgow Coma Scale score of 14 to 15). In the reversal group, patients received 34.3 units/kg activated PCC, 30.5 units/kg four-factor PCC, or 54.9 units/kg four-factor PCC and activated PCC on average. There was no difference observed in the incidence of hemorrhage progression (10.8% NR vs. 15.0% reversal; p = 0.739) or in median change in ICH volume (0 mL NR vs. 1 mL reversal; p = 0.2199) between groups. Additionally, reversal did not affect in-hospital mortality (3 [7.1%] NR vs. 4 [9.5%] reversal; p > 0.999). One patient in the reversal group developed a deep vein thrombosis (DVT) during the hospitalization; however, this did not result in a statistically significant difference in the occurrence of DVT (p > 0.999). CONCLUSIONS: This study demonstrated that PCC used for the treatment of factor Xa inhibitor-associated ICH related to mild TBI did not significantly impact the incidence or degree of hemorrhage progression, and PCC treatment did not result in increased thromboembolic events.

Impact of Pharmacist Education on Incoming Medical Residents.

Introduction: The graduating medical student transitioning to the role of a first-year medical resident is expected to know the proper medications and dosages for routine patient conditions. Pharmacists on an interdisciplinary health care team can be effective teachers of medical residents. Given the small amount of pharmacy-based education included in medical school curricula, it is important that medical residents have a basic foundation of pharmacotherapeutic knowledge. The purpose of this study was to assess the effectiveness of a pharmacist-led education session in improving medical resident pharmacotherapy knowledge. Methods: During orientation in 2016 to 2019, first-year medical residents completed an 8-item pre-test assessing their choices of medications and dosages on 8 patient conditions. A post-test assessing these same items was taken after a 50-minute lecture from a pharmacist experienced in resident education. First-year medical residents at a separate institution within the university system completed the pre-test only. Results: Overall, 243 medical residents received the lecture and took both tests and 170 medical residents at the other institution completed the pre-test only (100% response rate). Using descriptive statistics, the 2 groups of medical residents were comparable in age, gender, and scores on the pre-test. Medical residents receiving the lecture showed an average 32% point change improvement in performance on the post-test. The pharmacist-led lecture consistently received the highest ratings (4.7 ± 0.5 out of 5) from residents of all the orientation topics presented. Conclusions: A pharmacist-led education session increased the pharmacotherapy knowledge of first-year medical residents at their resident orientation. Medical residents value reinforcement of basic pharmacotherapy knowledge to start their training.

23.4% Sodium Chloride Versus Mannitol for the Reduction of Intracranial Pressure in Patients With Traumatic Brain Injury: A Single-Center Retrospective Cohort Study.

BACKGROUND: Intermittent doses of mannitol or hypertonic saline are recommended to treat elevated intracranial pressure (ICP). However, it is unclear if one agent is more effective than the other. Previous studies have compared mannitol and hypertonic saline in reduction of ICP, with conflicting results. However, no study thus far has compared 23.4% sodium chloride with mannitol. OBJECTIVE: The objective of this study was to determine the difference in absolute reduction of ICP 60 minutes after infusion of 23.4% sodium chloride versus mannitol. METHODS: This was a single-center retrospective cohort study that included patients at least 16 years old admitted to the trauma/surgical intensive care unit between August 8, 2016, and August 30, 2018, who received either 23.4% sodium chloride 30 mL and/or mannitol 0.5 g/kg and had an ICP monitor or external ventricular drain in place. The primary outcome was absolute reduction in ICP 60 minutes after infusion of hyperosmolar therapy. RESULTS: In all, 31 patients and 162 doses of hyperosmolar therapy were included in the analysis. There was no statistically significant difference in the primary end point of absolute reduction of ICP 60 minutes after infusion of hyperosmolar therapy comparing 23.4% sodium chloride 30 mL with 0.5 g/kg mannitol (P = 0.2929). There was no statistically significant difference found for any secondary end points. CONCLUSION AND RELEVANCE: No difference was found for absolute reduction of ICP at 30, 60, and 120 minutes, respectively, after infusion of hyperosmolar agent or time to next elevated ICP. Patient-specific parameters should be used to guide the choice of hyperosmolar agent to be administered.

Quetiapine for delirium prophylaxis in high-risk critically ill patients.

BACKGROUND: Delirium is common in patients admitted to the surgical trauma intensive care unit (ICU), and the risk factors for these patients differ from medical patients. Given the morbidity and mortality associated with delirium, efforts to prevent it may improve patient outcomes, but previous efforts pharmacologically have been limited by side effects and insignificant results. We hypothesized that scheduled quetiapine could reduce the incidence of delirium in this population. METHODS: The study included 71 adult patients who were at high-risk for the development of delirium (PRE-DELIRIC Score ≥50%, history of dementia, alcohol misuse, or drug abuse). Patients were randomized to receive quetiapine 12.5 mg every 12 h for delirium or no pharmacologic prophylaxis within 48 h of admission to the ICU. The primary end point was the incidence of delirium during admission to the ICU. Secondary end points included time to onset of delirium, ICU and hospital length of stay (LOS), ICU and hospital mortality, duration of mechanical ventilation, and adverse events. RESULTS: The incidence of delirium during admission to the ICU was 45.5% (10/22) in the quetiapine group and 77.6% (38/49) in the group that did not receive pharmacological prophylaxis. The mean time to onset of delirium was 1.4 days for those who did not receive prophylaxis versus 2.5 days for those who did (p = 0.06). The quetiapine group significantly reduced ventilator duration from 8.2 days to 1.5 days (p = 0.002). CONCLUSIONS: The findings suggested that scheduled, low-dose quetiapine is effective in preventing delirium in high-risk, surgical trauma ICU patients.

A Retrospective Cohort Analysis of the Use of Enteral Nutrition Plus Pharmacologic Prophylaxis or Enteral Nutrition Alone.

Background: Due to the risk of development of stress ulcers in intensive care unit (ICU) patients, pharmacologic prophylaxis is often utilized. However, some literature describes the use of enteral nutrition instead as stress ulcer prophylaxis. Methods: The purpose of this study is to determine if enteral nutrition is similar to pharmacologic stress ulcer prophylaxis (SUP) with enteral nutrition for reduction of gastrointestinal (GI) bleeding, perforation, or ulceration in ICU patients. This was a retrospective, single-center cohort study that took place at an academic medical center. Adult ICU patients receiving enteral nutrition who had a risk factor for stress-related mucosal damage were included. The primary outcome was the incidence of GI bleeding, perforation, or ulcer formation. Results: Overall, 167 patients were included in the study, 147 in the pharmacologic prophylaxis plus EN group (PPEN) and 20 in the enteral therapy only (EN) group. Of 167 patients included, 22 patients (21 in the PPEN group and 1 in the EN group) developed a primary outcome of GI bleeding, perforation, or ulceration (14.3% vs 5%, P = .4781). Patients in the PPEN group had a higher incidence of pneumonia (42.2% vs 15%, P = .0194), but no difference was seen between groups when patients with pneumonia present on admission were excluded (20.6% vs 10.5%, P = .5254). Conclusion: In this small cohort of patients, enteral nutrition alone is as effective as pharmacologic therapy in addition to enteral nutrition for the reduction of stress-related GI bleeding, perforation, and ulceration.

Identification of Risk Factors for Refractory Status Epilepticus.

Objective: The objective of this study is to identify risk factors for the development of refractory status epilepticus (RSE). Methods: This was an IRB-approved, retrospective case control study that included patients admitted with status epilepticus between August 1, 2014, and July 31, 2017. Cases were defined as those with RSE, and controls were those who did not develop RSE. A bivariate analysis was conducted comparing those with RSE and those without RSE. A stepwise logistic regression model was constructed predicting for progression to RSE. Risk factors for progression to RSE were extrapolated from this model. Results: A total of 184 patients met inclusion criteria for the study (99 controls and 49 cases). After adjusting for covariates in the logistic regression, patients with convulsive seizures had a lower odds of developing RSE (odds ratio [OR] = 0.375; 95% CI = 0.148 to 0.951; P = 0.0388). Treatment with benzodiazepines plus levetiracetam had a higher odds of developing RSE (OR = 3.804; 95% CI = 1.523 to 9.499; P = 0.0042). Conclusion and Relevance: This study found that patients with convulsive seizures had a lower odds of developing RSE. In addition, patients treated with benzodiazepines and levetiracetam had a higher odds of developing RSE. This information can be used to potentially identify patients at higher risk of developing RSE, so that treatment can be modified to reduce morbidity and mortality. These results may warrant further investigation into the effectiveness of levetiracetam as a first-line agent for the treatment of SE.

Melatonin, Ramelteon, Suvorexant, and Dexmedetomidine to Promote Sleep and Prevent Delirium in Critically Ill Patients: A Narrative Review With Practical Applications.

Sleep plays an important role in the recovery of critically ill patients. However, patients in the intensive care unit (ICU) often suffer sleep disturbances and abnormal circadian rhythms, which may increase delirium and lengthen ICU stay. Nonpharmacologic strategies for preventing and treating sleep disturbances and delirium, such as overnight eye masks and ear plugs, are usually employed first, given the lack of adverse effects. However, a multimodal approach to care including pharmacotherapy may be necessary. Despite the limited available data supporting their use, medications such as melatonin, ramelteon, suvorexant, and dexmedetomidine may promote sleep and improve a variety of patient-centric outcomes such as delirium. This narrative review focuses on these nonbenzodiazepine agents used for sleep in the ICU. Practical application of each of these agents is described for when providers choose to utilize one of these pharmacotherapies to promote sleep or prevent delirium.

Impact of the Sequence of Norepinephrine and Vasopressin Discontinuation in Patients Recovering From Septic Shock.

Background: Septic shock is a serious medical condition affecting millions of people each year and guidelines direct vasopressor use in these patients. However, there is little information as to which vasopressor should be discontinued first. Objective: The objective of this study was to assess the impact of the sequence of norepinephrine and vasopressin discontinuation on intensive care unit (ICU) length of stay. Methods: This was a single-center retrospective cohort study conducted at The University of Tennessee Medical Center in Knoxville, Tennessee. Patients included in this study were adults 18 years of age and older with a diagnosis of septic shock who received norepinephrine in combination with vasopressin. Patients were excluded if norepinephrine or vasopressin were not the last 2 vasoactive agents used or if the patient expired or care was withdrawn. Measurements and Main Results: A total of 86 patients were included in this study, with 34 patients in the norepinephrine discontinued first group (NDF) and 52 in the vasopressin discontinued first group (VDF). For the primary outcome of ICU length of stay, no statistically significant difference was found between the NDF and the VDF groups (9.38 days vs 11.07 days, P = .313). The secondary outcome of the dose of norepinephrine at which vasopressin was initiated was also found to not be significant between the NDF and VDF groups (22 µg/min vs 31.1 µg/min, P = .11). The rates of hypotension within 24 hours of discontinuation of the first agent were also not significant between the NDF and VDF groups (17% vs 31%, P = .38). Conclusions: Based on the results of this study, there was significant no difference in ICU length of stay based on the sequence of discontinuation between norepinephrine and vasopressin in patients recovering from septic shock.

Contrast-Induced Nephropathy in Ischemic Stroke Patients Undergoing Computed Tomography Angiography: CINISter Study.

GOAL: Computed tomography angiography (CTA) is a well-tolerated, noninvasive study of the intracranial vascular circulation; however, contrast-induced nephropathy (CIN) has been reported in 5%-7% of patients undergoing CTA. Limited studies have evaluated the risks of CIN in patients undergoing CTA. Our study was designed to evaluate the prevalence and risk factors for CIN in patients with ischemic stroke who receive a CTA. MATERIALS AND METHODS: Single-center, nested, case-control study of patients with ischemic stroke who received a CTA between June 18, 2012 and January 1, 2016. Patients were grouped based on development of CIN. FINDINGS: A total of 209 patients were included in the final analysis (178 controls, 31 cases). The prevalence of CIN during the time period studied was 14.8% (95% confidence interval [CI]: 10.2-20.2). A higher proportion of patients who developed CIN had a history of diabetes mellitus (37 [20.56%] versus 15 [48.39%]; P = .0009) and reported taking no medications prior to admission (35 [19.44%] versus 11 [35.48%]; P = .0458). However, a lower proportion of patients who developed CIN had a history of smoking (59 [32.78] versus 3 [9.68]; P = .0091). After statistical adjustment, only a history of diabetes (odds ratio [OR] 4.15 [95% CI: 1.765, 9.754), taking no medications prior to admission (OR 3.56 [95% CI: 1.417, 8.941]) and a self-reported history of smoking (OR 0.204 [95% CI: 0.057, 0.721]) remained associated with the development of CIN. CONCLUSIONS: Those patients with a history of diabetes mellitus or not taking medications prior to admission should be monitored closely for the development of contrast-induced nephropathy CIN.

Evaluation of Intravenous Acetaminophen on Length of Stay in Abdominal Surgery Patients.

Purpose: The objective of this study is to evaluate the effect of intravenous acetaminophen on length of stay (LOS) in abdominal surgery patients. Methods: This retrospective, cohort chart review evaluated patients who underwent colon resection or pancreaticoduodenectomy between January 1, 2010 and August 31, 2013. The primary outcome is postoperative LOS. Secondary outcomes include opioid use, pain scores, and naloxone or laxative use. Patients who received intravenous acetaminophen were compared to patients who did not. Results: A total of 329 patients were included, with 269 in the non-acetaminophen group compared to 60 patients in the acetaminophen group. There was no difference in postoperative LOS (9.2 s vs 9.1 days; P = .90). Postoperative LOS was also similar when controlling for surgery type. The acetaminophen group had reduced opioid consumption in the first 24 hours postoperatively (P = .02). However, pain scores were higher in the acetaminophen group, both in the first 24 hours (P = .007) and throughout the hospital stay (P < .001). Other clinical outcomes were similar between groups. Conclusion: Intravenous acetaminophen was not associated with a decreased postoperative LOS at our institution.

Management of apixaban-associated subdural hematoma: a case report on the use of factor eight inhibitor bypassing activity.

OBJECTIVE: We report a case of a patient receiving apixaban who developed a spontaneous subdural hematoma and declining mental status that improved after administration of a single dose of factor eight inhibitor bypassing activity. DESIGN: Case report. SETTING: Comprehensive Stroke Center, Neurocritical Care Unit. PATIENT: A 76-year-old man presented to an outside facility with a chief complaint of headache and pain behind his right eye. A CT scan of his head revealed a subdural hematoma. The patient was transferred to our facility with worsening clinical status. INTERVENTIONS: After a confirmatory cranial CT scan revealed a worsening subdural hematoma with midline shift, a single dose of factor VIII inhibitor bypassing activity (25 U/kg) was administered. MEASUREMENTS AND MAIN RESULTS: Coagulation tests following the administration of factor VIII inhibitor bypassing activity and a follow-up CT scan confirmed hemostasis. The patient was discharged home with no focal deficits. CONCLUSIONS: Factor VIII inhibitor bypassing activity may be a viable, nonspecific reversal agent for life-threatening bleeding associated with apixaban.

Interstitial pneumonitis from treatment with gemcitabine.

INTRODUCTION: The use of gemcitabine may lead to numerous adverse effects ranging from mild to very severe, such as interstitial pneumonitis. The diagnosis of this complication is based on multiple laboratory findings, radiographic evidence, and high clinical suspicion. Presented is a case report of a patient who met these criteria and had onset consistent with drug-induced interstitial pneumonitis. CASE PRESENTATION: A 76-year-old White female was treated with gemcitabine for pancreatic cancer. Two months after the initiation of therapy, she was admitted to the hospital for worsening dyspnea and cough. High clinical suspicion, bilateral interstitial opacities on chest x-ray, worsening pulmonary status, and onset 2 months after initiation of therapy led to the diagnosis of gemcitabine-induced interstitial pneumonitis. Steroid therapy with prednisone was initiated, and the patient's clinical symptoms and radiographic findings improved. DISCUSSION: Gemcitabine-induced interstitial pneumonitis is well described in the literature. It is a rare but serious complication associated with gemcitabine therapy in which patients present with worsening dyspnea. Most patients only require supportive care and discontinuation of the drug for treatment, but in severe cases supplemental oxygen and steroid therapy must be used before resolution of symptoms. It is important to obtain an accurate medication history to evaluate for other potentially pulmonary toxic medications. Radiographic findings such as bilateral infiltrates should be completely resolved after therapy. CONCLUSION: Radiographic findings, clinical symptoms, and clinical suspicion can lead to early recognition of interstitial pneumonitis from gemcitabine. Physician awareness of this adverse effect and early recognition are keys to providing prompt treatment in resolving symptoms and decreasing mortality.

Outcomes Associated With Levetiracetam Use After Spontaneous Intracerebral Hemorrhage.

Background and Purpose: The purpose of this study was to assess the incidence of seizures in patients with spontaneous intracerebral hemorrhage (ICH) who received prophylactic levetiracetam. Methods: This was a retrospective cohort study evaluating the use of levetiracetam in patients without a history of seizures who experienced a spontaneous intracerebral hemorrhage. Patients were excluded if they were younger than 18 years of age, had a documented history of a seizure disorder, or had an antiseizure drug documented on their home medication list. Patients were based on their exposure to levetiracetam. The primary outcome was incidence of seizure during hospital admission. Secondary outcomes included occurrence of adverse events, intensive care unit (ICU) length of stay (LOS), and hospital LOS. Results: Of the 229 patients included in the final analysis, 21 were in the levetiracetam group (LEV) and 208 were in the no levetiracetam group (no LEV). No statistical difference in seizure incidence was observed when comparing the LEV and no LEV groups (1 [4.8%] LEV vs 3 [1.4%] no LEV; P = .32). There was also no statistical difference in the median ICU LOS (2 days [1 day, 5 days] LEV vs 2 days [1 day, 3 days] no LEV; P = .27), median hospital LOS (6 days [2 days, 8 days] LEV vs 6 days [3 days, 9 days] no LEV; P = .27), or adverse events. Conclusions: This study does not support the use of levetiracetam prophylaxis in patients who have experienced an ICH.

Low Dose Aspirin Initiation 18 Hours After Thrombolytic Therapy in Acute Ischemic Stroke.

OBJECTIVES: To investigate the safety of administering low-dose aspirin (81 mg) 18 hours after intravenous thrombolytic therapy. METHODS: This is a retrospective cohort investigation. Individuals received either alteplase or tenecteplase for acute ischemic stroke followed by aspirin 81 mg (after follow-up imaging). An institutional change moved follow-up post-thrombolytic CT scans to 18 hours, and qualifying patients were grouped based on whether they received aspirin ≤24 hours or >24 hours. Chart reviews were conducted to assess the primary outcome of new or worsening intracranial hemorrhage, as well as secondary outcomes of change in stroke scale scores at discharge and 3 months, lengths of stay, favorable outcomes at 3 months, hospital readmission, and mortality. RESULTS: Out of 350 patients screened, 130 qualified for inclusion-50 of whom received aspirin ≤24 hours (mean 21.1 hours, SD±6.2), and 80 who received aspirin >24 hours (mean 34 hours, SD±8.2). Only 1 new intracranial bleed occurred following aspirin administration in the >24-hour group. No statistically significant differences were observed in any of the secondary outcomes, although there was higher mortality (3/50 vs. 2/80, P=0.372) and shorter hospital length of stay (median difference -1.0 day, P=0.0336) in the <24 hours group. CONCLUSIONS: Low-dose aspirin administration sooner than 24 hours following thrombolytic therapy did not increase bleeding events. Sooner aspirin administration after ischemic stroke can potentially enhance the prevention of secondary embolization and did not demonstrate worse clinical outcomes; however, further randomized controlled trials are needed.

Managing Modern Antiretroviral Therapy in the Intensive Care Unit: Overcoming Challenges for Critically Ill People With Human Immunodeficiency Virus.

People with human immunodeficiency virus (HIV) have a 50% excess risk for intensive care unit (ICU) admission, often for non-HIV-related conditions. Despite this, clear guidance for managing antiretroviral therapy (ART) in this setting is lacking. Selecting appropriate ART in the ICU is complex due to drug interactions, absorption issues, and dosing adjustments. Continuing ART in the ICU can be challenging due to organ dysfunction, drug interactions, and formulary limitations. However, with careful consideration, continuation is often feasible through dose adjustments or alternative administration methods. Temporary discontinuation of ART may be beneficial depending on the clinical scenario. Clinicians should actively seek resources and support to mitigate adverse events and drug interactions in critically ill people with HIV. Navigating challenges in the ICU can optimize ART and improve care and outcomes for critically ill people with HIV. This review aims to identify strategies for addressing the challenges associated with the use of modern ART in the ICU.

High-Risk Non-ST Elevation Acute Coronary Syndrome Outcomes in Patients Treated with Unfractionated Heparin Monitored Using Anti-Xa Concentrations Versus Activated Partial Thromboplastin Time.

BACKGROUND: While the activated partial thromboplastin time (aPTT) is the most widely used assay to monitor unfractionated heparin (UFH), providing a general measure of the extent of anticoagulation, it does not reliably correlate with the blood concentration of heparin or its antithrombotic effect. While cost and availability have limited the widespread use of UFH in hospitals, monitoring UFH with heparin levels has been shown to reduce both the number of monitoring tests and the time to a therapeutic range. OBJECTIVES: To compare outcomes in patients with non-ST elevation acute coronary syndrome (ACS) treated with weight-based UFH monitored with anti-Xa concentrations versus aPTT. METHODS: A retrospective chart review was completed in patients admitted with high-risk ACS and compared to the UFH arm of the SYNERGY trial. The primary outcome included the clinical endpoint of all-cause death or non-fatal myocardial infarction until time of hospital discharge. Safety endpoints evaluated included incidence of stroke and major bleeding. RESULTS: The primary endpoint occurred in 6.3% of patients in the study cohort compared to 6.5% of patients in the heparin arm of the SYNERGY trial at 48 hours (P = .006). Bleeding was reduced in the study cohort with a significant decrease in GUSTO severe bleeding (P = .007). Additionally the study cohort had significantly fewer patients with an absolute drop in hemoglobin or hematocrit. Thrombolysis in Myocardial Infarction (TIMI) major and minor bleeding, rate of transfusion, and platelet counts were similar between groups. CONCLUSIONS: Outcomes for high-risk ACS patients receiving heparin monitored by anti-Xa concentrations are noninferior to heparin monitored by aPTT.