Safety Profile of High-Dose Intravenous Push Lacosamide.

Lacosamide (LCM) is an antiseizure medication used to manage status epilepticus (SE). Previous retrospective analyses have demonstrated safety and efficiency in intravenous push (IVP) administration at 80 mg per minute. Quick administration can be achieved in a high-acuity setting without the additional time required for compounding. However, previous literature only partially represents high doses of IVP LCM, which limits the understanding of the safety profile of these doses. Our study was a single-center, retrospective, single-arm analysis of patients who received IVP LCM 300 mg or 400 mg during admission. The primary outcome was the incidence of infusion site reactions, hypotension, and bradycardia within 2 hours of IVP administration. Secondary outcomes included the incidence of PR prolongation. A total of 113 patients were evaluated for infusion site reactions. Of these, 108 patients had vital signs assessed within 2 hours of IVP LCM and could be evaluated for hypotension and bradycardia. The sample primarily consisted of LCM 400 mg IVP (85.8%). The primary outcome consisted of 7 (6.2%) infusion reactions, 12 (11.1%) hypotensive events, and no reports of bradycardia. Each adverse event was assessed using the Naranjo Adverse Drug Probability Scale. All events scored less than two, suggesting the possibility was likely related to factors other than the medication. In conclusion, LCM 300 mg and 400 mg IVP administration have the potential to facilitate more rapid treatment of seizures without additional risk of infusion site reactions, hypotension, and bradycardia.

Safety of early antiplatelet administration in patients with acute ischemic stroke treated with alteplase (SEAPT-24).

OBJECTIVES: Alteplase, a tissue-type plasminogen activator, is recommended for ischemic stroke patients presenting within 4.5 h. Due to bleeding risks, current guidelines advise delaying antiplatelet therapy for 24 h after alteplase. However, specific scenarios may require antiplatelet therapy to be given within the 24 h window. This study aimed to examine the safety of early antiplatelet therapy administration within the first 24 h after alteplase. MATERIALS AND METHODS: This study is a retrospective, observational study of adult patients with acute ischemic stroke who received alteplase across a multi-hospital system. Patients were grouped based on early antiplatelet therapy (within 24 h window) or as recommended per guidelines. The occurrence of bleeding events, including symptomatic intracranial hemorrhage and/or gastrointestinal bleeding, in-hospital mortality, unfavorable outcomes (modified Rankin score 3-6), and hospital length of stay, were compared between groups. RESULTS: Patients were predominantly African American (72%) and female (53%) with a median age of 62 years. Median baseline NIHSS scores were higher in the early group (5 vs. 7; p = 0.04), and patients in the early group were more likely to undergo endovascular therapy (26% vs. 8%, p < 0.0001). In patients treated with alteplase only and who did not undergo endovascular therapy, there was no difference in symptomatic intracranial hemorrhage (1.4% vs. 0%, p = 0.1), gastrointestinal bleeding, in-hospital mortality, unfavorable outcomes, or length of stay. CONCLUSIONS: In our retrospective analysis, early administration of antiplatelet therapy (< 24 h post-alteplase) did not increase the risk of symptomatic intracranial hemorrhage, gastrointestinal bleeding, or unfavorable outcomes in patients who received alteplase alone for management of acute ischemic stroke. Prospective studies are needed to validate these findings.

Safety of Propofol When Used for Rapid Sequence Intubation in Septic Patients: A Multicenter Cohort Study.

Purpose: Septic patients are at risk for hypotension, and this risk may increase during rapid sequence intubation (RSI). Sedatives such as propofol must be used carefully due to its ability to reduce vascular sympathetic tone. Since the safety of propofol for RSI is not well described in sepsis, this was a study evaluating propofol and its effects on hemodynamics when used for RSI in a septic population. Materials and methods: We conducted a multicenter, retrospective, cohort study of patients with sepsis or severe sepsis requiring sedation for RSI. Patients receiving a propofol bolus for RSI were compared to patients undergoing RSI without a propofol bolus. The safety profile of propofol was evaluated according to the rates of post-intubation hypotension and vasopressor utilization between groups. Results: A total of 179 patients (79 propofol, 100 non-propofol) were evaluated. There were no differences in hypotension (81% vs 78%; P = .62) or vasopressor utilization between the propofol and non-propofol groups (43% vs 49%; P = .43). Patients in the non-propofol group had increased APACHE II scores and healthcare-associated infections. Conclusions: In this cohort study, administration of propofol for RSI in patients with sepsis and severe sepsis did not increase incidence of hypotension or vasopressor use, but acute illness may have introduced provider selection bias causing less propofol use in the non-propofol group. Larger prospective studies are needed to better characterize the adverse hemodynamic effects of propofol, before propofol bolus doses for RSI can be considered for safe use in this population.

Evaluation of the Safety of Rapid Administration of Undiluted High-Dose Intravenous Levetiracetam.

Background: Intravenous (IV) levetiracetam (LEV) is an antiseizure medication traditionally given as an intermittent infusion to mitigate potential adverse effects given its acidic formulation. The process of compounding may lead to delays in treating status epilepticus, which is why administration of undiluted doses is of interest. Prior studies have shown safety of IV doses from 1000 mg to 4500 mg; however, assessments of adverse side effects outside IV site reactions have not been studied. Methods: A retrospective analysis was completed with patients who received 1500 mg doses of undiluted IV LEV. We included patients ≥ 18 years old that received at least 1 dose of IV LEV 1500 mg from January 2018 to February 2021. Study end points included assessment of hemodynamic disturbance (bradycardia [HR less than 50 beats per minute] or hypotension [SBP less than 90 mmHg] within 1 hour or documented infusion reaction within 12 hours of LEV. Descriptive statistics were utilized. Results: A total 213 doses of 1500 mg of IV LEV were administered to 107 patients. Peripheral lines were used for 85.9% of doses. Approximately half of doses (57) were administered to patients on the general wards, with the remainder in the intensive care unit or emergency department. Two patients (1.9%) experienced bradycardia; however, 1 patient had pre-existing bradycardia. Three patients (3.8%) experienced hypotension; however, those patients were receiving vasopressors prior to the dose. There were no cases of infusion reaction. Conclusion: Undiluted, rapid administration of IV LEV 1500 mg was well tolerated and safe.

Use of Prothrombin Complex Concentrate in Oral Anticoagulant-Associated Major Bleeding.

Severe bleeding remains the most significant adverse effect associated with both warfarin and the direct oral anticoagulant agents. Due to the life-threatening nature of these bleeds, knowledge and understanding of agents that are able to rapidly overcome the anticoagulation effects of these medications is paramount to their use. Worldwide, the most commonly used agent for this indication is prothrombin complex concentrate (PCC). This review summarizes the evidence on the use of PCC in this population and provides practical information regarding patient-specific administration considerations.

Effect of desmopressin acetate on acute spontaneous intracranial hemorrhage in patients on antiplatelet therapy.

PURPOSE: To evaluate the impact of desmopressin acetate (DDAVP) on poor outcomes, hematoma expansion, and adverse events in patients diagnosed with a non-traumatic, antiplatelet-associated intracranial hemorrhage (ICH). METHODS: This was a multicenter, retrospective, propensity-matched cohort study comparing DDAVP to control in patients diagnosed with a non-traumatic ICH previously on antiplatelet therapy. Notable exclusion criteria included admission to trauma service, subarachnoid hemorrhages, confounding coagulopathic factors, and hematoma evacuation. Poor outcome, defined as discharge to hospice or in-patient mortality, was the primary outcome. Secondary outcomes included intracranial hematoma expansion and occurrence of adverse events, which included hyponatremia and thromboembolic events. RESULTS: A total of 49 patients receiving DDAVP were compared to 107 controls in the unmatched cohort. Thirty-seven patients treated with DDAVP and 55 controls were included in the propensity-matched analysis, which was adjusted for age, ethnicity, history of diabetes, receipt of platelet transfusion, and thromboembolism prophylaxis. Poor outcome (16.2% DDAVP vs 29% control, p = 0.13), rates of hematoma expansion (11.8% DDAVP vs 11.1% control, p = 0.99), and adverse events (21.6% DDAVP vs 20% control, p = 0.99) were statistically similar between the matched groups. CONCLUSIONS: DDAVP administration in patients with spontaneous antiplatelet-associated ICH was not associated with a reduction in poor outcomes, hematoma expansion, or an increase in adverse events. Use of DDAVP in this patient population appears to be safe. Larger prospective studies are warranted to evaluate DDAVP utility in this patient population.

Predictors of dysrhythmias with norepinephrine use in septic shock.

PURPOSE: Norepinephrine (NE) is recommended first-line for treatment of septic shock, partly due to its intrinsically low effect on heart rate. While dysrhythmias secondary to NE are still reported, factors associated with development of this adverse effect have not been described. Our study sought to investigate factors associated with dysrhythmias in patients receiving NE for septic shock. MATERIALS AND METHODS: We conducted a retrospective cohort study of adults receiving NE for septic shock if NE was initiated as the first vasopressor and continued for at least 6 h. The primary objective was to determine the rate of dysrhythmias among this patient population. Secondary objectives included determining the effect of dysrhythmia development on patient outcomes and elucidating predictors for dysrhythmia development. RESULTS: Of the 250 patients included, 34.4% (n = 86) developed a dysrhythmia. These patients had higher mortality (30.5% vs. 63.9%; p < 0.001) with decreased ICU-free days (2 vs. 4; p = 0.04) and ventilator-free days (7 vs. 4; p = 0.048). Duration of NE infusion and maximum NE dose were found to be independently associated with increased rates of dysrhythmia (p < 0.005). CONCLUSION: Development of dysrhythmia is associated with increased mortality and is independently associated with longer duration of NE infusion and higher NE doses.

A retrospective, observational study of perampanel in refractory and super-refractory status epilepticus.

INTRODUCTION: The outcomes of administration of Perampanel (PER) which is a ß-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propionic acid (AMPA) receptor antagonist for the treatment of refractory status epilepticus (RSE) and Super-refractory (SRSE) were previously reported in small cohort studies and case reports. We report efficacy and side effect results of an observational cohort of 75 patients treated with PER for RSE and SRSE. METHODS: This was a single-center, retrospective, observational study of patients with RSE admitted to the neurocritical care unit between April 2017 and September 2019 who received treatment with PER. The primary outcome was the occurrence of a definite response to PER, which was defined as clear resolution of the ictal pattern and/or seizures within 72 h of delivery of PER which was the last administered antiseizure medication (ASM). Secondary outcomes included the percentage of patients other response types (partial responder or non-responder), as well as the rate of adverse effects. RESULTS: A total 75 patients were included in our analysis. PER was initiated as the median sixth ASM at a median initial dose of 12 mg. For the primary outcome, 31 (41.3%; 95% confidence interval 31.0%-53.0%) patients were classified as a definite responder. Seven patients (9.3%) experienced an adverse effect that was attributed to PER, with the most common being sedation in four patients. CONCLUSIONS: In our retrospective cohort of RSE, we observed a definite response rate of 41.3% within 72 h of PER initiation. PER was well tolerated with few documented adverse effects. Further prospective studies are needed to confirm the role of PER in treating patients with RSE.

An Association Between Hyperchloremia and Acute Kidney Injury in Patients With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: While an association between hyperchloremia and worse outcomes, such as acute kidney injury and increased mortality, has been demonstrated in hemorrhagic stroke, it is unclear whether the same relationship exists after acute ischemic stroke. This study aims to determine the relationship between moderate hyperchloremia (serum chloride ≥115 mmol/L) and acute kidney injury in patients with ischemic stroke. METHODS: This is a multicenter, retrospective, propensity-matched cohort study of adults admitted for acute ischemic stroke. The primary objective was to determine the relationship between moderate hyperchloremia and acute kidney injury, as defined by the Acute Kidney Injury Network criteria. Secondary objectives included mortality and hospital length of stay. RESULTS: A total of 407 patients were included in the unmatched cohort (332 nonhyperchloremia and 75 hyperchloremia) and 114 patients (57 in each group) were matched based upon propensity scores. In the matched cohort, hyperchloremia was associated with an increased risk of acute kidney injury (relative risk 1.91 [95% confidence interval 1.01-3.59]) and a longer hospital length of stay (16 vs 12 days; P = .03). Mortality was higher in the hyperchloremia group (19.3% vs 10.5%, P = .19), but this did not reach statistical significance. CONCLUSIONS: In this study, hyperchloremia after ischemic stroke was associated with increased rates of acute kidney injury and longer hospital length of stay. Further research is needed to determine which interventions may increase chloride levels in patients with acute ischemic stroke and the association between hyperchloremia and clinical outcomes.

Effect of Alteplase Administration on International Normalized Ratio in Patients With Acute Ischemic Stroke.

BACKGROUND/OBJECTIVE: Alteplase may elevate international normalized ratio (INR) results, although the exact rate of elevation occurrence is not firmly established in the literature. The purpose of this study is to determine the occurrence rate of INR elevation following alteplase administration. We also aimed to determine what factors are independently associated with the development of elevated INR following alteplase administration for ischemic stroke. METHODS: We conducted a multicenter, retrospective, cohort study of patients who received alteplase for acute ischemic stroke. Patients were screened for baseline INR measurement and a repeat value within 24 hours of alteplase administration. The primary outcome was the percent of patients who experienced ≥0.4-point increase in INR. Secondary outcomes included the rate of adverse bleeding events and identification of factors independently associated with elevated INR following alteplase administration. RESULTS AND CONCLUSIONS: Two hundred and sixty-one patients were included, with 44 (16.9%) patients having an INR increase of 0.4 or more. Patients with an INR increase ≥0.4 experienced a nonstatistically significant increase in bleeding episodes (8.8% vs 18.2%; P = .10). We identified African American race (odds ratio, 3.48, 95% confidence interval, 1.5-7.6; P = .002) as an independent predictor of INR increase ≥0.04. An INR elevation is common following receipt of alteplase for ischemic stroke. Those of African American race were at increased risk of INR elevation; however, more studies are needed to determine whether these patients are at a higher bleeding risk as a result of INR elevation.

A Retrospective Comparison of 3-Factor Prothrombin Complex Concentrate Products for Warfarin Reversal.

BACKGROUND AND PURPOSE: Current guidelines suggest that 3-factor prothrombin complex concentrate is a possible alternative to 4-factor products for the emergent reversal of bleeding secondary to warfarin. While multiple observational studies have evaluated various forms of 3-factor prothrombin complex concentrate individually, no study has compared the efficacy of the 2 products. The purpose of this study is to compare the efficacy and safety of Bebulin™ and Profilnine™ for the emergent reversal of warfarin-associated major bleeding. METHODS: We conducted a retrospective cohort study of patients receiving both Bebulin™ and Profilnine™ at an urban, academic medical center with comprehensive stroke center designation and a neurosurgical center of excellence. All patients were treated at a single center that utilized a fixed, weight-based dosing protocol. The primary outcome was the percentage of patients in each group achieving a goal international normalization ratio of 1.4 or less. RESULTS: There was a significant difference in goal international normalization ratio achieved favoring Bebulin™ (85.5% vs 27.3%; P < .001) over Profilnine™. Median dose per kilogram of actual body weight was the same between the groups. When we assessed results by baseline™ international normalization ratio subgroup, more patients in the Bebulin™ group achieved goal when baseline values were 6 or less. No thrombotic events were documented in either group. CONCLUSIONS: We found that patients treated with Bebulin™ experienced significantly higher rates of successful international normalization ratio reversal when compared to those who received Profilnine™. Further research is needed to determine the comparative efficacy between the 2 agents.

Predicting Surgical Intervention in Cerebellar Stroke: A Quantitative Retrospective Analysis.

BACKGROUND: Debate still exists regarding whether preventive surgical decompression should be offered to high-risk patients experiencing cerebellar stroke. This study aimed to predict neurologic decline based on risk factors, volumetric analysis, and imaging characteristics. METHODS: This retrospective cohort study comprised patients ≥18 years who presented with acute cerebellar ischemic stroke (CIS) between January 2011 and December 2016. Diagnostic imaging was used to calculate metrics based on individual stroke, cerebellar, and posterior fossa volumes. Head computed tomography scans on presentation and day of peak swelling were used to tabulate a CIS score. RESULTS: The study included 86 patients; most were male and African American. Posterior inferior communicating artery stroke was most common (50%). On initial presentation imaging, 18.6% had documented hydrocephalus, 20.9% had brainstem compression, 22.1% had brainstem stroke, and 39.5% had stroke in another vascular territory. Cardioembolic stroke was the most common etiology, followed by cryptogenic stroke. Overall, patients who underwent surgical intervention had larger stroke volumes on presentation. Patients undergoing surgical intervention also experienced faster cerebellar swelling compared with patients without intervention. Total CIS scores were statistically significant and remained significant on the peak day of swelling. CIS score was independently associated with neurosurgical intervention; patients in this group with delayed interventions (median CIS score, 6; range, 4-8) later deteriorated and required emergent surgical decompression. Eleven patients without intervention had CIS score >6; 4 patients died of stroke complications. CONCLUSIONS: Volumetric studies and CIS score are objective measures that may help predict decline on imaging before clinical deterioration.

Factor Xa Inhibitor-Related Intracranial Hemorrhage: Results From a Multicenter, Observational Cohort Receiving Prothrombin Complex Concentrates.

BACKGROUND: Since the approval of the oral factor Xa inhibitors, there have been concerns regarding the ability to neutralize their anticoagulant effects after intracranial hemorrhage (ICH). Multiple guidelines suggest using prothrombin complex concentrates (PCCs) in these patients on the basis of research that includes a limited number of patients with ICH. Given this, we aimed to evaluate the safety and efficacy of PCCs for factor Xa inhibitor-related ICH in a large, multicenter cohort of patients. METHODS: This was a multicenter, retrospective, observational cohort study of patients with apixaban- or rivaroxaban-related ICH who received PCCs between January 1, 2015, and March 1, 2019. The study had 2 primary analysis groups: safety and hemostatic efficacy. The safety analysis evaluated all patients meeting inclusion criteria for the occurrence of a thrombotic event, which were censored at hospital discharge or 30 days after PCC administration. Patients with intracerebral, subarachnoid, or subdural hemorrhages who had at least 1 follow-up image within 24 hours of PCC administration were assessed for hemostatic efficacy. The primary efficacy outcome was the percentage of patients with excellent or good hemostasis on the basis of the modified Sarode criteria. Secondary outcomes included an evaluation of in-hospital mortality, length of stay, infusion-related reactions, and thrombotic event occurrence during multiple predefined periods. RESULTS: A total of 663 patients were included and assessed for safety outcomes. Of these, 433 patients met criteria for hemostatic efficacy evaluation. We observed excellent or good hemostasis in 354 patients (81.8% [95% CI, 77.9-85.2]). Twenty-five (3.8%) patients had a total of 26 thrombotic events, of which 22 occurred in the first 14 days after PCC administration. One patient had documentation of an infusion-related reaction. For the full cohort of patients, in-hospital mortality was 19.0%, and the median intensive care unit and hospital lengths of stay were 2.0 and 6.0 days, respectively. CONCLUSIONS: Administration of PCCs after apixaban- and rivaroxaban-related ICH provided a high rate of excellent or good hemostasis (81.8%) coupled with a 3.8% thrombosis rate. Randomized, controlled trials evaluating the clinical efficacy of PCCs in patients with factor Xa inhibitor-related ICH are needed.

Blood Pressure Management Following Acute Ischemic Stroke: A Review of Primary Literature.

Elevated blood pressure is common in patients with acute ischemic stroke. While this may occur secondary to the body's own response to preserve cerebral blood flow, elevated blood pressure may also increase the risk of hemorrhagic transformation. Current guidelines recommend various blood pressure goals based upon multiple factors, including thresholds specific to certain treatment interventions. Despite these guidelines, there is limited evidence to support specific blood pressure targets, and variability in clinical practice is common. The purpose of this review was to discuss blood pressure management in adult patients with acute ischemic stroke, focusing on appropriate targets in the setting of alteplase administration, mechanical thrombectomy, and hemorrhagic transformation.

Thiamine Use in Sepsis: B1 for Everyone?

Every year, sepsis affects nearly 30 million people worldwide, with current annual estimates reporting as many as 6 million deaths. To combat the staggering number of patients who are affected by sepsis, clinicians continue to investigate novel treatment approaches. One treatment approach that has gained interest is the role that vitamins and nutrients play in the body's response to sepsis. Thiamine, in particular, has been studied because of its role in glucose metabolism and lactate production. This review provides a summary of the current literature surrounding the use of thiamine in the treatment of sepsis and describes the function of this essential nutrient in sepsis pathology. We also aim to provide clinicians with the necessary understanding to recognize the potential for thiamine deficiency, as well as detail the role of thiamine supplementation in the treatment of sepsis.

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.

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.