Symptomatic intracranial hemorrhage (sICH) is the most feared complication of intravenous thrombolytic therapy in acute ischemic stroke. Treatment of sICH is based on expert opinion and small case ...series, with the efficacy of such treatments not well established. This document aims to provide an overview of sICH with a focus on pathophysiology and treatment.
A literature review was performed for randomized trials, prospective and retrospective studies, opinion papers, case series, and case reports on the definitions, epidemiology, risk factors, pathophysiology, treatment, and outcome of sICH. The document sections were divided among writing group members who performed the literature review, summarized the literature, and provided suggestions on the diagnosis and treatment of patients with sICH caused by systemic thrombolysis with alteplase. Several drafts were circulated among writing group members until a consensus was achieved.
sICH is an uncommon but severe complication of systemic thrombolysis in acute ischemic stroke. Prompt diagnosis and early correction of the coagulopathy after alteplase have remained the mainstay of treatment. Further research is required to establish treatments aimed at maintaining integrity of the blood-brain barrier in acute ischemic stroke based on inhibition of the underlying biochemical processes.
Objective
The aim was to investigate whether intensive blood pressure treatment is associated with less hematoma growth and better outcome in intracerebral hemorrhage (ICH) patients who received ...intravenous nicardipine treatment ≤2 hours after onset of symptoms.
Methods
A post‐hoc exploratory analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH‐2) trial was performed. This was a multicenter, international, open‐label, randomized clinical trial, in which patients with primary ICH were allocated to intensive versus standard blood pressure treatment with nicardipine ≤4.5 hours after onset of symptoms. We have included 913 patients with complete imaging and follow‐up data in the present analysis.
Results
Among the 913 included patients, 354 (38.7%) had intravenous nicardipine treatment initiated within 2 hours. In this subgroup of patients treated within 2 hours, the frequency of ICH expansion was significantly lower in the intensive blood pressure reduction group compared with the standard treatment group (p = 0.02). Multivariable analysis showed that ultra‐early intensive blood pressure treatment was associated with a decreased risk of hematoma growth (odds ratio, 0.56; 95% confidence interval CI, 0.34–0.92; p = 0.02), higher rate of functional independence (odds ratio, 2.17; 95% CI, 1.28–3.68; p = 0.004), and good outcome (odds ratio, 1.68; 95% CI, 1.01–2.83; p = 0.048) at 90 days. Ultra‐early intensive blood pressure reduction was associated with a favorable shift in modified Rankin Scale score distribution at 3 months (p = 0.04).
Interpretation
In a subgroup of ICH patients with elevated blood pressure given intravenous nicardipine ≤2 hours after onset of symptoms, intensive blood pressure reduction was associated with reduced hematoma growth and improved functional outcome. ANN NEUROL 2020;88:388–395.
Summary Background Rapid reversal of vitamin K antagonist (VKA)-induced anticoagulation is often necessary for patients needing urgent surgical or invasive procedures. The optimum means of VKA ...reversal has not been established in comparative clinical trials. We compared the efficacy and safety of four-factor prothrombin complex concentrate (4F-PCC) with that of plasma in VKA-treated patients needing urgent surgical or invasive procedures. Methods In a multicentre, open-label, phase 3b randomised trial we enrolled patients aged 18 years or older needing rapid VKA reversal before an urgent surgical or invasive procedure. We randomly assigned patients in a 1:1 ratio to receive vitamin K concomitant with a single dose of either 4F-PCC (Beriplex/Kcentra/Confidex; CSL Behring, Marburg, Germany) or plasma, with dosing based on international normalised ratio (INR) and weight. The primary endpoint was effective haemostasis, and the co-primary endpoint was rapid INR reduction (≤1·3 at 0·5 h after infusion end). The analyses were intended to evaluate, in a hierarchical fashion, first non-inferiority (lower limit 95% CI greater than −10% for group difference) for both endpoints, then superiority (lower limit 95% CI >0%) if non-inferiority was achieved. Adverse events and serious adverse events were reported to days 10 and 45, respectively. This trial is registered at ClinicalTrials.gov , number NCT00803101. Findings 181 patients were randomised (4F-PCC n=90; plasma n=91). The intention-to-treat efficacy population comprised 168 patients (4F-PCC, n=87; plasma, n=81). Effective haemostasis was achieved in 78 (90%) patients in the 4F-PCC group compared with 61 (75%) patients in the plasma group, demonstrating both non-inferiority and superiority of 4F-PCC over plasma (difference 14·3%, 95% CI 2·8–25·8). Rapid INR reduction was achieved in 48 (55%) patients in the 4F-PCC group compared with eight (10%) patients in the plasma group, demonstrating both non-inferiority and superiority of 4F-PCC over plasma (difference 45·3%, 95% CI 31·9–56·4). The safety profile of 4F-PCC was generally similar to that of plasma; 49 (56%) patients receiving 4F-PCC had adverse events compared with 53 (60%) patients receiving plasma. Adverse events of interest were thromboembolic adverse events (six 7% patients receiving 4F-PCC vs seven 8% patients receiving plasma), fluid overload or similar cardiac events (three 3% patients vs 11 13% patients), and late bleeding events (three 3% patients vs four 5% patients). Interpretation 4F-PCC is non-inferior and superior to plasma for rapid INR reversal and effective haemostasis in patients needing VKA reversal for urgent surgical or invasive procedures. Funding CSL Behring.
It is unclear whether intensive lowering of blood pressure (BP) at the acute phase of intracerebral haemorrhage (ICH) is beneficial. We performed a meta-analysis of randomised controlled trials ...(RCTs) to assess whether intensive BP lowering in patients with acute ICH is safe and effective in improving clinical outcomes.
We searched PubMed, EMBASE and the Cochrane databases for relevant RCTs and calculated pooled OR for 3-month mortality (safety outcome) and 3-month death or dependency (modified Rankin Scale (mRs) ≥3;efficacy outcome), in patients with acute ICH randomised to either intensive BP-lowering or standard BP-lowering treatment protocols. We also investigated the association between treatment arm and ICH expansion at 24 hours. Random effects models with DerSimonian-Laird weights were used.
Five eligible studies including 4360 patients with acute ICH were pooled in meta-analysis. The risk of 3-month mortality was similar between patients randomised to intensive BP-lowering treatment and standard BP-lowering treatment (OR: 0.99; 95% CI: 0.82 to 1.20, p=0.909). Intensive BP-lowering treatment showed a (non-significant) trend for an association with lower 3-month death or dependency risk compared with standard treatment (OR: 0.91; 95% CI: 0.80 to 1.02), p=0.106). Intensive BP reduction was associated with a trend for lower risk of significant ICH expansion compared with standard treatment (OR: 0.82; 95% CI: 0.68 to 1.00, p=0.056), especially in larger RCTs.
For patients with acute ICH similar to those included in RCTs and without contraindication to acute BP treatment, intensive acute BP lowering is safe, but does not seem to provide an incremental clinical benefit in terms of functional outcomes. The effect of intensive BP lowering on significant haematoma expansion at 24 hours warrants further investigation.
Right ventricular failure (RVF) increases morbidity and mortality. The RECOVER RIGHT study evaluated the safety and efficacy of a novel percutaneous right ventricular assist device, the Impella RP ...(Abiomed, Danvers, MA), in a prospective, multicenter trial.
Thirty patients with RVF refractory to medical treatment received the Impella RP device at 15 United States institutions. The study population included 2 cohorts: 18 patients with RVF after left ventricular assist device (LVAD) implantation (Cohort A) and 12 patients with RVF after cardiotomy or myocardial infarction (Cohort B). The primary end point was survival to 30 days or hospital discharge (whichever was longer). Major secondary end points included indices of safety and efficacy.
The patients (77% male) were a mean age of 59 ± 15 years, 53% had diabetes, 88.5% had a history of congestive heart failure, and 37.5% had renal dysfunction. Patients were on an average of 3.2 inotropes/pressors. Device delivery was achieved in all but 1 patient. Hemodynamics improved immediately after initiation of Impella RP support, with an increase in cardiac index from 1.8 ± 0.2 to 3.3 ± 0.23 liters/min/m(2) (p < 0.001) and a decrease in central venous pressure from 19.2 ± 4 to 12.6 ± 1 mm Hg (p < 0.001). Patients were supported for an average of 3.0 ± 1.5 days (range, 0.5-7.8 days). The overall survival at 30 days was 73.3%. All patients discharged were alive at 180 days.
In patients with life-threatening RVF, the novel percutaneous Impella RP device was safe, easy to deploy, and reliably resulted in immediate hemodynamic benefit. These data support its probable benefit in this gravely ill patient population.
Intracerebral hemorrhage (ICH) is the deadliest type of stroke and up to half of patients die in hospital. Blood pressure management, coagulopathy reversal, and intracranial pressure control are the ...mainstays of acute ICH treatment. Prevention of hematoma expansion and minimally invasive hematoma evacuation are promising therapeutic strategies under investigation. This article provides an updated review on ICH diagnosis and management in the emergency department.
Patients experiencing major bleeding while taking vitamin K antagonists require rapid vitamin K antagonist reversal. We performed a prospective clinical trial to compare nonactivated 4-factor ...prothrombin complex concentrate (4F-PCC) with plasma for urgent vitamin K antagonist reversal.
In this phase IIIb, multicenter, open-label, noninferiority trial, nonsurgical patients were randomized to 4F-PCC (containing coagulation factors II, VII, IX, and X and proteins C and S) or plasma. Primary analyses examined whether 4F-PCC was noninferior to plasma for the coprimary end points of 24-hour hemostatic efficacy from start of infusion and international normalized ratio correction (≤1.3) at 0.5 hour after end of infusion. The intention-to-treat efficacy population comprised 202 patients (4F-PCC, n=98; plasma, n=104). Median (range) baseline international normalized ratio was 3.90 (1.8-20.0) for the 4F-PCC group and 3.60 (1.9-38.9) for the plasma group. Effective hemostasis was achieved in 72.4% of patients receiving 4F-PCC versus 65.4% receiving plasma, demonstrating noninferiority (difference, 7.1% 95% confidence interval, -5.8 to 19.9). Rapid international normalized ratio reduction was achieved in 62.2% of patients receiving 4F-PCC versus 9.6% receiving plasma, demonstrating 4F-PCC superiority (difference, 52.6% 95% confidence interval, 39.4 to 65.9). Assessed coagulation factors were higher in the 4F-PCC group than in the plasma group from 0.5 to 3 hours after infusion start (P<0.02). The safety profile (adverse events, serious adverse events, thromboembolic events, and deaths) was similar between groups; 66 of 103 (4F-PCC group) and 71 of 109 (plasma group) patients experienced ≥1 adverse event.
4F-PCC is an effective alternative to plasma for urgent reversal of vitamin K antagonist therapy in major bleeding events, as demonstrated by clinical assessments of bleeding and laboratory measurements of international normalized ratio and factor levels.
http://www.clinicaltrials.gov. Unique identifier: NCT00708435.
To evaluate whether the burden of deep and lobar lacunes differs between patients with intracerebral hemorrhage (ICH) with definite/probable cerebral amyloid angiopathy (CAA) per the Boston criteria ...and hypertensive small vessel disease (HTN-SVD; ICH in basal ganglia, thalami, brainstem).
We defined lobar and deep lacunes similar to the topographic distribution used for ICH and cerebral microbleeds (CMBs). We then compared their distribution between patients with CAA-ICH and those with strictly deep CMB and ICH (HTN-ICH). The independent associations of lacune location with the diagnosis of CAA-ICH and HTN-ICH were evaluated with multivariable models. The relationship between lobar lacunes and white matter hyperintensity (WMH) volume was evaluated by means of partial correlation analyses adjusted for age and a validated visual scale.
In our final cohort of 316 patients with ICH, lacunes were frequent (24.7%), with similar rates in 191 patients with CAA and 125 with HTN-ICH (23% vs 27.2%,
= 0.4). Lobar lacunes were more commonly present in CAA (20.4% vs 5.7%,
< 0.001), while deep lacunes were more frequent in HTN-ICH (15.2% vs 2.1%,
< 0.001). After correction for demographics and clinical and neuroimaging markers of SVD, lobar lacunes were associated with CAA (
= 0.003) and deep lacunes with HTN-ICH (
< 0.001). Lobar lacunes in 80% of the cases were at least in contact with WMH, and after adjustment for age, they were highly correlated to WMH volume (
= 0.42,
< 0.001).
Lobar lacunes are associated with CAA, whereas deep lacunes are more frequent in HTN-SVD. Lobar lacunes seem to have a close relationship with WMH, suggesting a possible common origin.
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