scholarly journals Clinical Strategies Against Early Hematoma Expansion Following Intracerebral Hemorrhage

2021 ◽  
Vol 15 ◽  
Author(s):  
Kanta Tanaka ◽  
Kazunori Toyoda
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Stroke Onset ◽  
Factor Vii ◽  
Hematoma Expansion ◽  
Thrombin Inhibitor ◽  
Small Magnitude ◽  
Hematoma Enlargement ◽  
Significant Difference ◽  
Hematoma Growth

Hematoma volume is the strongest predictor of morbidity and mortality after intracerebral hemorrhage. Protection against early hematoma growth is therefore the mainstay of therapeutic intervention for acute intracerebral hemorrhage, but the current armamentarium is restricted to early blood pressure lowering and emergent reversal for anticoagulant agents. Although intensive lowering of systolic blood pressure to <140 mmHg appears likely to prevent hematoma growth, two recent randomized trials, INTERACT-2 and ATACH-2, demonstrated non-significant trends of reduced hematoma enlargement by intensive blood pressure control, with only a small magnitude of benefit or no benefit for clinical outcomes. While oral anticoagulants can be immediately reversed by prothrombin complex concentrate, or the newly developed idarucizumab for direct thrombin inhibitor or andexanet for factor Xa inhibitors, the situation regarding reversal of antiplatelet agents is not yet quite as advanced. However, considering at most the approximately 10% rate of anticoagulant use among patients with intracerebral hemorrhage, what is most essential for patients with intracerebral hemorrhage in general is early hemostatic therapy. Tranexamic acid may safely reduce hematoma expansion, but its hemostatic effect was insufficient to be translated into improved functional outcomes in the TICH-2 randomized trial with 2,325 participants. In this context, recombinant activated factor VII (rFVIIa) is a candidate to be added to the armory against hematoma enlargement. The FAST, a phase 3 trial that compared doses of 80 and 20 μg/kg rFVIIa with placebo in 841 patients within 4 h after the stroke onset, showed a significant reduction in hematoma growth with rFVIIa treatment, but demonstrated no significant difference in the proportion of patients with severe disability or death. However, a post hoc analysis of the FAST trial suggested a benefit of rFVIIa in a target subgroup of younger patients without extensive bleeding at baseline when treated earlier after stroke onset. The FASTEST trial is now being prepared to determine this potential benefit of rFVIIa, reflecting the pressing need to develop therapeutic strategies against hematoma enlargement, a powerful but modifiable prognostic factor in patients with intracerebral hemorrhage.

Early Achievement of Blood Pressure Lowering and Hematoma Growth in Acute Intracerebral Hemorrhage: Stroke Acute Management with Urgent Risk-Factor Assessment and Improvement-Intracerebral Hemorrhage Study

2018 ◽  
Vol 46 (3-4) ◽  
pp. 116-122
Author(s):  
Yoshitaka Yamaguchi ◽  
Masatoshi Koga ◽  
Shoichiro Sato ◽  
Hiroshi Yamagami ◽  
Kenichi Todo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Risk Factor ◽  
Intracerebral Hemorrhage ◽  
Acute Management ◽  
Acute Hypertension ◽  
Risk Factor Assessment ◽  
Significant Difference ◽  
Pressure Lowering ◽  
Hematoma Growth ◽  
Multicenter Prospective Observational Study

Background: Previous studies have revealed that hematoma growth mainly occurs during the first 6 h after the onset of spontaneous intracerebral hemorrhage (ICH). Early lowering of blood pressure (BP) may be beneficial for preventing hematoma growth. However, relationships between timing of BP lowering and hematoma growth in ICH remain unclear. We investigated associations between timing of BP lowering and hematoma growth for ICH. Methods: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study was a multicenter, prospective, observational study investigating the safety and feasibility of early (within 3 h from onset) reduction of systolic BP (SBP) to < 160 mm Hg with intravenous nicardipine for acute hypertension in cases of spontaneous ICH. The present study was a post hoc analysis of the SAMURAI-ICH study. We examined relationships between time from onset, imaging, and initiation of treatment to target SBP achievement and hematoma growth (absolute growth ≥6 mL) in ICH patients. Target SBP achievement was defined as the time at which SBP first became < 160 mm Hg. Results: Among 211 patients, hematoma growth was seen in 31 patients (14.7%). The time from imaging to target SBP and time from treatment to target SBP were significantly shorter in patients without hematoma growth than in those with (p = 0.043 and p = 0.032 respectively), whereas no significant difference was seen in time from onset to SBP < 160 mm Hg between groups (p = 0.177). Patients in the lower quartiles of time from imaging to target SBP and time from treatment to target SBP showed lower incidences of hematoma growth (p trend = 0.023 and 0.037 respectively). The lowest quartile of time from imaging to target SBP (< 38 min) was negatively associated with hematoma growth on multivariable logistic regression (OR 0.182; 95% CI 0.038–0.867; p = 0.032). Conclusions: Early achievement of target SBP < 160 mm Hg is associated with a lower risk of hematoma growth in ICH.

Abstract WP347: Early Achievement of Blood Pressure Lowering on Hematoma Growth in Hyperacute Intracerebral Hemorrhage: the SAMURAI-ICH Study

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Yoshitaka Yamaguchi ◽  
Masatoshi Koga ◽  
Kenichi Todo ◽  
Shoichiro Sato ◽  
Hiroshi Yamagami ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Antihypertensive Treatment ◽  
Blood Pressure Lowering ◽  
Acute Hypertension ◽  
Negatively Associated ◽  
Significant Difference ◽  
Pressure Lowering ◽  
Hematoma Growth ◽  
Multicenter Prospective Observational Study

Background: Little has been investigated about associations between timing of blood pressure lowering and clinical outcome of intracerebral hemorrhage (ICH). Methods: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study is a multicenter, prospective, observational study investigating the safety and feasibility of early (within 3 hours from symptom onset) systolic blood pressure (SBP) reduction to less than 160 mmHg with intravenous nicardipine for acute hypertension in patients with spontaneous ICH. We retrospectively examined the relationship between time from onset, CT imaging, and initiation of antihypertensive treatment to target SBP achievement and hematoma growth in ICH patients. Hematoma growth was defined as an absolute growth of ≥ 6 ml from baseline to second imaging at 24 (±6) hours after the initiation of antihypertensive treatment. Results: Among 211 patients (81 women (38.4%), mean age 66 years), mean baseline hematoma volume was 13 ml and hematoma growth was seen in 36 (17.1%) patients. Time from image to target SBP and time from treatment to target SBP were significantly shorter in patients without hematoma growth than those with ( P = 0.043 and P = 0.032, respectively), whereas there was not significant difference in time from onset to target SBP between the two groups ( P = 0.177). Lower quartiles of time from image to target SBP and time from treatment to target SBP had lower incidences of hematoma growth (P trend = 0.023 and 0.037, respectively, Cochran-Armitage test), whereas there was not significant trend in time from onset to target SBP ( P = 0.074). The lowest quartile of time from image to target SBP was negatively associated with hematoma growth on multivariate logistic regression (odds ratio 0.182, 95% confidential interval 0.038-0.867, P = 0.032). Conclusions: Early achievement to target SBP <160 mmHg was negatively associated with hematoma growth in ICH patients.

Abstract WP305: Impact of Potential Systolic Blood Pressure Treatment Thresholds on Hematoma Growth in Acute Intracerebral Hemorrhage

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
David Rodriguez-Luna ◽  
Marta Rubiera ◽  
Marian Muchada ◽  
Pilar Coscojuela ◽  
Marc Ribo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Systolic Blood Pressure ◽  
Statistical Significance ◽  
Secondary Analysis ◽  
Hematoma Enlargement ◽  
Treatment Thresholds ◽  
Hematoma Growth ◽  
Acute Intracerebral Hemorrhage ◽  
The Impact

Background: Although the current AHA guidelines recommend maintaining systolic blood pressure (SBP) below 180 mmHg in acute intracerebral hemorrhage (ICH), little is known about the relationships between different therapeutic target thresholds and hematoma growth (HG). Therefore, we aimed to investigate the impact of potential SBP treatment thresholds on HG in patients with acute ICH. Methods: This study was a secondary analysis of data prospectively collected during a previously reported study of the impact of blood pressure (BP) on HG in 106 patients with acute (<6 hours) supratentorial ICH. Patients underwent baseline and 24-hour computed tomography scans, and noninvasive BP monitoring at 15 minutes interval over first 24 hours. SBP loads were defined as the percentage of 24-hour SBP monitoring values exceeding 140, 150, 160, 170, 180, 190, and 200 mmHg. HG was defined as a relative enlargement greater than 33% or an absolute expansion more than 6 mL at 24 hours. Results: Patients who experienced HG (34%) presented higher SBP loads in all thresholds, reaching statistical significance in 170, 180, and 190 thresholds, but not in the others (Figure). Whilst SBP load thresholds were correlated neither with baseline nor 24-hour ICH volumes, highest (170 to 200) but not lowest (140 to 160) SBP load thresholds were significantly correlated with the amount of both relative and absolute hematoma enlargement at 24 hours (p<0.05). In multivariate analyses, both SBP 170-load (OR 1.034, 95% CI 1.001-1.070, p=0.048) and 180-load (OR 1.052, 95% CI 1.010-1.097, p=0.016) were independently related to HG. Conclusions: In patients with acute supratentorial ICH, those who experience HG present higher SBP load from 140 to 200 mmHg thresholds. More intensive SBP-lowering treatment than guidelines recommendations is needed, at least below 170 mmHg, in order to minimize the deleterious effect of higher SBP on HG.

scholarly journals Acute hypertensive response in patients with intracerebral hemorrhage pathophysiology and treatment

2017 ◽  
Vol 38 (9) ◽  
pp. 1551-1563 ◽  
Author(s):  
Adnan I Qureshi ◽  
Mushtaq H Qureshi
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Systolic Blood Pressure ◽  
Cerebral Hemorrhage ◽  
Blood Pressure Reduction ◽  
Systemic Blood Pressure ◽  
Current Evidence ◽  
Hematoma Expansion ◽  
Pressure Reduction ◽  
Small Magnitude

Acute hypertensive response is a common systemic response to occurrence of intracerebral hemorrhage which has gained unique prominence due to high prevalence and association with hematoma expansion and increased mortality. Presumably, the higher systemic blood pressure predisposes to continued intraparenchymal hemorrhage by transmission of higher pressure to the damaged small arteries and may interact with hemostatic and inflammatory pathways. Therefore, intensive reduction of systolic blood pressure has been evaluated in several clinical trials as a strategy to reduce hematoma expansion and subsequent death and disability. These trials have demonstrated either a small magnitude benefit (second intensive blood pressure reduction in acute cerebral hemorrhage trial and efficacy of nitric oxide in stroke trial) or no benefit (antihypertensive treatment of acute cerebral hemorrhage 2 trial) with intensive systolic blood pressure reduction compared with modest or standard blood pressure reduction. The differences may be explained by the variation in intensity of systolic blood pressure reduction between trials. A treatment threshold of systolic blood pressure of ≥180 mm with the target goal of systolic blood pressure reduction to values between 130 and 150 mm Hg within 6 h of symptom onset may be best supported by current evidence.

Late Neurological Deterioration after Acute Intracerebral Hemorrhage: A post hoc Analysis of the ATACH-2 Trial

2020 ◽  
Vol 49 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Shuhei Okazaki ◽  
Haruko Yamamoto ◽  
Lydia D. Foster ◽  
Mayumi Fukuda-Doi ◽  
Masatoshi Koga ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Significant Risk ◽  
Blood Pressure Level ◽  
Neurological Deterioration ◽  
Major Influence ◽  
Case Report Form ◽  
Hematoma Volume ◽  
Systolic Blood Pressure Level ◽  
Significant Difference

Background: Neurological deterioration (ND) has a major influence on the prognosis of intracerebral hemorrhage (ICH); however, factors associated with ND occurring after 24 h of ICH onset are unknown. Methods: We performed exploratory analyses of data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial, which compared intensive and standard blood pressure lowering treatment in ICH. NDs were captured on the adverse event case report form. Logistic regression analysis was performed to examine the independent predictors of late ND. Results: Among 1,000 participants with acute ICH, 82 patients (8.2%) developed early ND (≤24 h), and 64 (6.4%) had late ND. Baseline hematoma volume (adjusted OR [aOR] per 1-cm3 increase 1.04, 95% CI 1.02–1.06, p < 0.0001), hematoma volume increase in 24 h (aOR 2.24, 95% CI 1.23–4.07, p = 0.008), and the presence of intraventricular hemorrhage (IVH; aOR 2.38, 95% CI 1.32–4.29, p = 0.004) were independent predictors of late ND (vs. no late ND). Late ND was a significant risk factor for poor 90-day outcome (OR 3.46, 95% CI 1.82–6.56). No statistically significant difference in the incidence of late ND was noted between the 2 treatment groups. Conclusions: Initial hematoma volume, early hematoma volume expansion, and IVH are independent predictors of late ND after ICH. Intensive reduction in the systolic blood pressure level does not prevent the development of late ND.

scholarly journals Lower Treatment Blood Pressure Is Associated With Greatest Reduction in Hematoma Growth After Acute Intracerebral Hemorrhage

Hypertension ◽  
2010 ◽  
Vol 56 (5) ◽  
pp. 852-858 ◽  
Author(s):  
Hisatomi Arima ◽  
Craig S. Anderson ◽  
Ji Guang Wang ◽  
Yining Huang ◽  
Emma Heeley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Lower Treatment ◽  
Hematoma Growth ◽  
Acute Intracerebral Hemorrhage

Abstract 3729: Delayed Hematoma Expansion Occurs After ICH: Observations from the Safety of Pioglitazone for Hematoma Resolution in INtraCerebral Hemorrhage (SHRINC) trial

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Navdeep S Sangha ◽  
Farhaan Vahidy ◽  
Mallikarjunarao Kasam ◽  
Mohammed Rahbar ◽  
Bursaw Andrew ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Prospective Study ◽  
Univariate Analysis ◽  
Primary Objective ◽  
Hematoma Expansion ◽  
Hematoma Growth ◽  
Secondary Objective ◽  
Magnetic Resonance Imaging Mri ◽  
Associated Risk Factors

Background and Purpose Early hematoma expansion (EHE) has been described in the first 48 hours. SHRINC is a phase 2 prospective safety trial whose primary objective is to assess the safety of pioglitazone (PIO) when administered to patients with spontaneous intracerebral hemorrhage (SICH) compared to standard care. A secondary objective is to characterize the changes in hematoma resolution and expansion over time. This prospective study addresses the natural history, clinical impact, and associated risk factors of late hematoma expansion (LEX) by serial magnetic resonance imaging (MRI) after SICH. Methods SHRINC aims to enroll 78 subjects between the ages of 18-80 with a SICH of ≥ 5 ml. This analysis includes the first 42 patients enrolled. Four subjects were excluded because they did not have an MRI after day 2. A baseline CTH was performed followed by an MRI within 24 hours of symptom onset. Hematoma volume (Hv) was measured on FLAIR sequences using a previously published semi-automated range of interest method. LEX was defined as an increase in Hv > 0.5 ml after the 48 hour MRI. Factors associated with LEX were evaluated with logistic regression. Longitudinal analyses were used for measurements taken over the follow up period. Results: Ten (26.3%) of 38 subjects displayed LEX. Eight subjects had LEX between day 2 to 14, and 4 between days 14 to 28. The median initial Hv was 16.1cc in LEX patients and 24.1cc in those without expansion (NEX) (p=0.23). Lower platelet counts (p=0.04) and BUN levels (p=0.03) were associated with LEX in univariate analysis. Multivariate analysis suggested that those with higher BUN levels were less likely to have LEX (OR=0.81; 95%CI 0.65-0.99). Blood pressure and EHE (13.2%) were not associated with LEX. There was no difference in neurological worsening (NIHSS increase ≥ 4), 6 month mRS or death between LEX and NEX. Conclusion: This is the first prospective study to address LEX with serial MRIs. LEX occurs between day 2 to 14 and day 14 to 28. Elevated BUN levels may decrease the likelihood of LEX. A limitation of our study is that the effect of PIO on LEX could not be evaluated because SHRINC is a blinded trial. Further studies will assess the pathophysiology of LEX and its potential implications in clinical trials evaluating hematoma growth and resolution.

Abstract W MP110: INR reversal of Oral Anticoagulant-Associated Intracerebral Hemorrhage

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Fernando Testai ◽  
Faisal Mukarram ◽  
Andrew Culpepper ◽  
Maureen Hillmann ◽  
Padmini Sekar ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Oral Anticoagulants ◽  
Case Fatality ◽  
Fresh Frozen Plasma ◽  
Factor Vii ◽  
Hematoma Expansion ◽  
Racial Variations ◽  
Fresh Frozen ◽  
Time And Being ◽  
Admission Variables

Background: The use of oral anticoagulants (OAC) is associated with poor outcome in intracerebral hemorrhage (ICH). In this study we investigated the effect of delayed INR reversal and the factors influencing it in patients with OAC-associated ICH (OAC-ICH). Methods: Data were obtained from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study which is a prospective, multi-ethnic multicenter study of ICH. Exclusion criteria included missing initial hematoma volume, INR or ED arrival time and being on heparin. Baseline characteristics, INR at baseline and 12h, hematoma location and volume, treatment received, hematoma expansion at 24h, and mortality at 3 months were recorded. INR reversal was defined as INR<1.4 at 12h post admission. Variables associated with INR reversal and case fatality at 3 months in non-OAC users and OAC users with and without INR <1.4 were compared. Results: A total of 1,746 of 2,276 subjects were included in the analysis. A higher proportion of OAC users (n=185) were white and had hypertension, diabetes, hypercholesterolemia, and lobar ICH than non-users (P<0.05). Baseline INRs for the OAC group were 3.1 (28.7%). Subjects on OAC received fresh frozen plasma (FFP, 44%) monotherapy, either recombinant factor VII or prothrombin complex (FVII/PCC, 7%), or a combination of FFP/FVII/PCC (11%). Increasing age (OR=0.96, 95% CI 0.94-0.98), elevated baseline INR (OR=0.34, 95% CI 0.26-0.43), and use of FFP only (OR=0.07, 95% CI 0.04-0.13) was associated with lack of INR reversal at 12h. Median INR at 12h (IQR) were 1.4 (1.3-1.6), 1.1 (0.9-1.1), and 1.0 (1.0-1.3) for the FFP, PCC/FVII, and FFP/FVII/PCC groups, respectively (p1.4 did not influence the rate of hematoma expansion at 24h. Case fatality at 3 months was 22% for non-OAC-ICH, 34% for OAC-ICH with INR<1.4, and 44% for OAC-ICH with INR>1.4 (p=.0005). Conclusion: In the ERICH study, patients treated with FFP monotherapy were less likely to have a normalized INR at 12h and this was associated with increased case fatality at 3 months. The use of FVII/PCC may shorten time to INR correction and improve outcome in OAC-ICH.

scholarly journals Regional differences in the response to acute blood pressure lowering after cerebral hemorrhage

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011229
Author(s):  
Kazunori Toyoda ◽  
Yuko Y Palesch ◽  
Masatoshi Koga ◽  
Lydia Foster ◽  
Haruko Yamamoto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Intracerebral Hemorrhage ◽  
East Asia ◽  
Functional Outcomes ◽  
Intensive Treatment ◽  
Hematoma Expansion ◽  
Blood Pressure Lowering ◽  
Pressure Lowering ◽  
Intensive Blood Pressure

Objective:To compare the impact of intensive blood pressure (BP) lowering right after intracerebral hemorrhage (ICH) on clinical and hematoma outcomes among patients from different geographic locations, we performed a prespecified sub-analysis of the randomized, multi-national, two-group, open-label trial to determine the efficacy of rapidly lowering BP in hyperacute ICH (ATACH-2), involving 537 patients from East Asia and 463 recruited outside of Asia.Methods:Eligible patients were randomly assigned to a systolic BP (SBP) target of 110-139 mmHg (intensive treatment) or 140-179 mmHg (standard treatment). Pre-defined outcomes were: poor functional outcome (modified Rankin Scale score of 4-6 at 90 days), death within 90 days, hematoma expansion at 24 hours; and cardio-renal adverse events within 7 days.Results:Poor functional outcomes (32.0% versus 45.9%), death (1.9% versus 13.3%), and cardio-renal adverse events (3.9% versus 11.2%) occurred significantly less in patients from Asia than those outside of Asia. The treatment-by-cohort interaction was not significant for any outcomes. Only patients from Asia showed a lower incidence of hematoma expansion with intensive treatment (adjusted RR 0.56, 95% CI 0.38-0.83). Both Asian (3.53, 1.28-9.64) and non-Asian cohorts (1.71, 1.00-2.93) showed a higher incidence of cardio-renal adverse events with intensive treatment.Conclusions:Poor functional outcomes and death 90 days after ICH were less common in patients from East Asia than those outside of Asia. Hematoma expansion, a potential predictor for poor clinical outcome, was attenuated by intensive BP lowering only in the Asian cohort.Clinicaltrials.gov identifierNCT01176565.Classification of evidence:This study provides Class II evidence that, for patients from East Asia with intracerebral hemorrhage, intensive blood pressure lowering significantly reduces the risk of hematoma expansion.

scholarly journals Earlier Blood Pressure-Lowering and Greater Attenuation of Hematoma Growth in Acute Intracerebral Hemorrhage

Stroke ◽  
2012 ◽  
Vol 43 (8) ◽  
pp. 2236-2238 ◽  
Author(s):  
Hisatomi Arima ◽  
Yining Huang ◽  
Ji Guang Wang ◽  
Emma Heeley ◽  
Candice Delcourt ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Blood Pressure Lowering ◽  
Pressure Lowering ◽  
Hematoma Growth ◽  
Acute Intracerebral Hemorrhage
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