Reviving Decades-Old Wisdom: Longitudinal Analysis of Renin-Angiotensin System Inhibitors and Its Effects on Acute Ischemic Stroke to Improve Outcomes.

BACKGROUND: While renin-angiotensin system (RAS) inhibitors have a longstanding history in blood pressure control, their suitability as first-line in-patient treatment may be limited due to prolonged half-life and kidney failure concerns. METHODS: Using a cohort design, we assessed the impact of RAS inhibitors, either alone or in combination with beta-blockers, on mortality, while exploring interactions, including those related to end-stage renal disease and serum creatinine levels. Eligible subjects were Acute Ischemic Stroke (AIS) patients aged 18 or older with specific subtypes who received in-patient antihypertensive treatment. The primary outcome was mortality rates. Statistical analyses included cross-sectional and longitudinal approaches, employing generalized linear models, G-computation, and discrete-time survival analysis over a 20-day follow-up period. RESULTS: In our study of 3,058 AIS patients, those using RAS inhibitors had significantly lower in-hospital mortality (2.2%) compared to non-users (12.1%), resulting in a relative risk (RR) of 0.18 (95% CI: 0.12-0.26). Further analysis using G-computation revealed a marked reduction in mortality risk associated with RAS inhibitors (0.0281 vs. 0.0913, risk difference [RD] of 6.31% or 0.0631, 95% CI: 0.046-0.079). Subgroup analysis demonstrated notable benefits, with individuals having creatinine levels below and above 1.3 mg/dl exhibiting statistically significant RD (RD -0.0510 vs. -0.0895), and a significant difference in paired comparison (-0.0385 or 3.85%, CI 0.023-0.054). Additionally, longitudinal analysis confirmed a consistent daily reduction of 0.93% in mortality risk associated with the intake of RAS inhibitors. CONCLUSIONS: RAS inhibitors are associated with a significant reduction in in-hospital mortality in AIS patients, suggesting potential clinical benefits in improving patient outcomes.

Is a minimum duration of 5 days of unfractionated heparin infusion necessary before transition to oral anticoagulation in cerebral venous thrombosis? a retrospective chart review.

In managing cerebral venous sinus thrombosis (CVT), the standard approach has been administering parenteral anticoagulation for at least five days, despite limited supporting evidence. This study aimed to determine the optimal duration of parenteral anticoagulation for CVT patients and its potential impact on their functional outcomes upon discharge. This retrospective observational cohort study was conducted across multiple healthcare centers and included adult CVT patients who received varying durations of parenteral anticoagulation: less than 5 days (n = 25) or 5 days or more (n = 16). The primary focus was on the duration of acute anticoagulation treatment, with secondary endpoints including hospital stay length and functional outcomes. The study found that a shorter duration of anticoagulation treatment (< 5 days) was linked to more favorable outcomes, as measured by the modified Rankin Scale (mRS) (68% vs. 25%, RR = 0.37, CI 0.15-0.90, p = 0.007). However, regression analysis showed non statistically significant associations for all variables except gender. Female patients were significantly more likely to receive a shorter duration of anticoagulation (Odds Ratio: 2.6, 95% CI: 2.2-3.1, P-Value: <0.001). These findings suggest a potential connection between shorter anticoagulation duration (< 5 days) and improved CVT patient outcomes, as indicated by their mRS scores at discharge. The observed relationship between female gender and shorter anticoagulation duration warrants further exploration. Nevertheless, caution is necessary when interpreting these findings due to the small sample size and specific patient characteristics. Further research in a larger and more diverse cohort is essential to validate these results and understand their implications fully.

Hemostatic efficacy of four factor prothrombin complex concentrate in intracerebral hemorrhage patients receiving warfarin vs. factor Xa inhibitors.

INTRODUCTION: 4-F PCC is administered for reversal of factor Xa inhibitor-associated coagulopathy despite a lack of quality evidence demonstrating hemostatic efficacy. The aim of this study was to evaluate the hemostatic efficacy of 4-F PCC in intracerebral hemorrhage patients who received factor Xa inhibitors versus warfarin. MATERIALS AND METHODS: This was a multi-center, retrospective, observational cohort study at a large healthcare system. Patients taking warfarin received 4-F PCC 25-50 units/kg based on the presenting INR, while patients taking a factor Xa inhibitor received 35 units/kg. The primary outcome was the percentage of patients with good or excellent hemostatic efficacy as assessed by modified Sarode scale, with neurologic outcomes assessed as a secondary endpoint. Patients were included in the primary outcome population if they had a repeat CT scan within 24 h. RESULTS: One hundred fifty-seven patients were included in the primary outcome population; [warfarin (n = 76), factor Xa inhibitors (n = 81)]. Hemostatic efficacy was 83 % in the warfarin group versus 75 % in the factor Xa inhibitor group (p = 0.24). The hemostatic efficacy risk difference between the groups was 7.6 % (95 % CI 5.1 %, 20.2 %). Good neurologic outcome (mRS 0-2) at discharge was 17 % in warfarin patients versus 12 % in the factor Xa inhibitor patients (p = 0.40). CONCLUSIONS: There was no significant difference in hemostatic efficacy or clinical outcomes between patients taking warfarin or a factor Xa inhibitor following reversal with 4-F PCC. This study provides further support that 4-F PCC can be used for the reversal of factor Xa inhibitor-associated coagulopathy.

Evaluation of the Use of Low-Dose 4-Factor Prothrombin Complex Concentrate in the Reversal of Direct Oral Anticoagulants in Bleeding Patients.

OBJECTIVE: This study investigated the percentage of patients who achieved hemostasis with 4-factor prothrombin complex concentrate (4-factor PCC) 35 U/kg. The primary end point was to determine the effect of 4-factor PCC 35 U/kg on bleeding progression, assessed using computed tomography. METHODS: This was a retrospective, observational, single-center study conducted in patients with a major bleed admitted to a level 1 trauma center from May 1, 2013, to June 15, 2015, who received 4-factor PCC 35 U/kg for reversal of a direct factor Xa inhibitor taken prior to admission. RESULTS: Thirty-three patients were included in the study, with 31 patients in the final analysis. The mean (standard deviation) age was 73 (14.8) years; 54.5% of patients were female. Of the 33 patients, 13 presented with a traumatic brain injury, 9 with an aneurysmal subarachnoid hemorrhage, 8 with an intracerebral hemorrhage, 1 with a gastrointestinal bleed, 1 with a hematoma with active extravasation, and 1 with an intra-abdominal bleed. The most frequently used direct factor Xa inhibitor was rivaroxaban (81.8%). Overall, 83.8% of patients achieved hemostasis with 4-factor PCC 35 U/kg. Progression of hemorrhage was observed in 4 patients on repeat computed tomography scan and 1 patient had continued surgical bleeding. No thromboembolic events were reported. CONCLUSIONS: Low-dose, 4-factor PCC 35 U/kg appeared to produce hemostasis in a majority of the patients. This may be an effective dosing regimen for anticoagulant reversal of factor Xa inhibitors in clinically bleeding patients.

Comparison of Clevidipine and Nicardipine for Acute Blood Pressure Reduction in Patients With Stroke.

OBJECTIVE: The aim of this study was to determine whether clevidipine (CLEV) achieved faster blood pressure control compared to nicardipine (NIC) in patients presenting with either an acute ischemic stroke (AIS) or a spontaneous intracerebral hemorrhage (ICH). METHODS: This was a retrospective, observational, cohort study conducted in patients with AIS or ICH admitted to the emergency department of a Comprehensive Stroke Center from November 2011 to June 2013 who received CLEV or NIC continuous infusion for acute blood pressure management. RESULTS: The study included 210 patients: 70 in the CLEV group and 140 in the NIC group. There was no difference in mean time (standard deviation [SD]) from initiation of the infusion to goal systolic blood pressure (SBP), CLEV: 50 (83) minutes versus NIC: 74 (103) minutes, P = .101. Comparison of the 2 agents within diagnosis showed no difference. Hypotension developed in 5 (7.1%) CLEV patients versus 14 (10%) NIC patients (P = .003). There was no difference in the percentage change at 2 hours; CLEV: -20% (16%) versus NIC: -16% (16%), P = .058. Mean (SD) time to alteplase administration from admission was 56 (22) minutes in the CLEV group versus 59 (25) minutes in the NIC group (P = .684). CONCLUSIONS: There was no difference in the mean time from initiation of the infusion to the SBP goal between agents or in the secondary outcomes. Due to the lack of differences observed, each agent should be considered based on the patient care needs of the institution.

Pharmacologic Management of Paroxysmal Sympathetic Hyperactivity After Brain Injury.

Paroxysmal sympathetic hyperactivity (PSH) is a result of acute brain injury that has been well known for many decades. However, the evidence for management of PSH is almost entirely anecdotal in nature. We reviewed case reports or series of pharmacotherapy management of PSH. These studies mentioned treatment options, but few studies exist to guide treatment strategies. For many years, the syndrome was not clearly understood; therefore, the therapy has focused on control of symptoms. In 2014, a Steering Committee came together to develop a conceptual definition and produced a consensus set of diagnostic criteria. Although understanding the diagnostic criteria is very well needed in management of patients with PSH, pharmacologic management is also crucial. Data describing the drug choices, dosing, and duration of therapy are also sparse. Recognition of appropriate medications is important because PSH is associated with morbidity, longer hospitalization, delaying transfer to rehabilitation units, and increasing cost. In this review article, we discussed the common medications used in the treatment of PSH. Treatment should target symptom abortion, prevention of symptoms, and refractory treatment. Symptom-abortive medications are indicated to control discrete breakthrough episodes, using medications such as morphine and short-acting benzodiazepines. Other medications used for prevention of symptoms and refractory treatment include long-acting benzodiazepines, nonselective ß-blockers, α2 agonists, opioids, and GABA agonists. The mechanisms by which these agents improve symptoms of PSH remain speculative. However, a combination of medications from different classes seems the most effective approach in managing PSH symptoms. There is wide variability in clinical practice with regard to drug choices, dosing, and duration of therapy. Future research needs to be conducted using the new PSH assessment measure to appropriately apply drug management.

High dose subcutaneous unfractionated heparin for prevention of venous thromboembolism in overweight neurocritical care patients.

Timing and dosing of chemical venous thromboembolism (VTE) prophylaxis in brain injury is controversial. Risk of bleeding while using high dose unfractionated heparin (UFH) in overweight patients to prevent VTE is also unknown. The purpose of this study was to describe the use of subcutaneous heparin 7500 units for VTE prophylaxis in overweight patients. This was a retrospective study comparing patients over 100 kg who received either 7500 units Q8 h (n = 141) (high dose group, HDG), or 5000 units Q8 h (n = 257) (traditional dose group, TDG), of UFH subcutaneously. Both groups had similar rates of bleeding complications. The incidence of drop in hemoglobin by two points in any 24 h was 14 % (20/141) HDG versus 11 % (28/257) TDG; P = 0.33. Hemoglobin drop by two points from baseline was 57 % (81/141) HDG versus 51 % (132/257) TDG; P = 0.24. The need for pRBC transfusion was 26 % (36/141) HDG versus 20 % (52/257) TDG; P = 0.22. An increase in aPTT from baseline by two times was 4 % (5/141) HDG versus 4 % (9/257) TDG, P = 0.59. Discontinuation of heparin therapy for association with progressive bleeding was not documented in any patients. No differences in minor bleeding complications were observed. There was no difference in the incidence of VTE: 5.7 % (8/141) HDG versus 9.3 % (24/257) TDG; P = 0.2. In univariate and multivariable logistic regression analysis, only the time of the initiation of heparin after admission was associated with the occurrence of VTE (median, IQR) 46 h (17-86) HDG versus 105 h (56-167) TDG; OR 1.2 (1.1-1.3); P < 0.001. High dose subcutaneous UFH was not associated with an increased risk of bleeding, nor did it decrease the incidence of VTE in overweight patients.

Advanced assessment of platelet function during adult donor care.

Abnormal platelet function may complicate the assessment and treatment of continuing blood loss, hypotension, and coagulation disorders during adult donor care. Antiplatelet drugs, such as aspirin, nonsteroidal anti-inflammatory drugs, clopidogrel (Plavix), ticlopidine (Ticlid), prasugrel (Effient), abciximab (ReoPro), eptifibatide (Integrilin), and tirofiban (Aggrastat) are commonly prescribed for older patients. These medications may be part of home therapy or may be given during acute cardiac or cerebrovascular crises that may lead to brain death and organ donation. This discussion reviews normal platelet formation and function, drug actions, methods to evaluate medication effects, pharmacological characteristics, treatment recommendations for platelet transfusion, and risks attendant with those infusions.

LOAD: a pilot study of the safety of loading of aspirin and clopidogrel in acute ischemic stroke and transient ischemic attack.

BACKGROUND: Most patients with ischemic stroke present to the emergency department beyond the approved 3-hour time window for thrombolytic or other revascularization therapies. Clopidogrel and aspirin loading is commonly used to prevent deterioration in other acute vascular occlusive events. This pilot study examined the safety of antiplatelet loading in acute ischemic stroke and transient ischemic attack. METHODS: Forty patients with stroke or transient ischemic attack symptoms, not eligible for revascularization, received a single dose of 375 mg of clopidogrel and 325 mg of aspirin within 36 hours of stroke onset. All patients were admitted to a comprehensive stroke department and monitored for neurologic deterioration (2-point increase on National Institutes of Health stroke scale [NIHSS] score) and bleeding complications until hospital day 7 or discharge. NIHSS was performed at 24 hours postadmission and on hospital day 7 or discharge, whichever came first. RESULTS: A total of 40 patients were loaded with 375 mg of clopidogrel and 325 mg of aspirin (mean 12 hours 32 minutes). Mean admission NIHSS score was 6. There were no cases of systemic hemorrhage or mortality. A single symptomatic intracranial hemorrhage (2.5%) was detected 43 hours posttreatment. When compared with matched control subjects, loaded patients were no more likely to experience hemorrhage and significantly less likely to experience neurologic deterioration (odds ratio 17.2; P < .002). CONCLUSIONS: Loading with 375 mg of clopidogrel and 325 mg of aspirin appears to be safe when administered up to 36 hours after stroke and transient ischemic attack onset in this pilot study. Neurologic deterioration may be decreased and warrants further study.

Bacterial infection during adult donor care.

Assessment, prevention, and treatment of bacterial infection in donors are critically important to the welfare of grafts and recipients after transplantation. Transmission of bacterial, viral, fungal, and protozoan infections from a donor to recipient(s) has been documented to have serious or fatal consequences. This article reviews issues of bacterial infection only. The organ procurement coordinator, supported by guidelines developed and prospectively modified by the organ procurement organization, must assess the donor for the presence and severity of bacterial tissue invasion and administer appropriate antimicrobial agents during donor care. Continuation of infection control measures, obtaining serial or surveillance samples for culture, review of antibiotic sensitivity data, initiation of empiric treatment, and modification of medications or their dosing are components of this important responsibility during donor care.

Cardiac dysrhythmias during donor care.

Organ procurement coordinators must treat various cardiac dysrhythmias (arrhythmias), including rhythm disturbances that may cause or follow a cardiac arrest, in about 15% to 50% of donors. Treatment decisions should be based on the particular dysrhythmia and its effect on donor blood pressure. Medications selected should be effective but short acting. In this article, data available in publications located through a PubMed search are reviewed and specific dysrhythmias that are likely to occur during donor care are described. Treatment recommendations are based on guidelines from the American Heart Association.