Intensive blood pressure lowering in patients with acute cerebral hemrrhage

Intensive Blood Pressure lowering in Patients with acute cerebral hemorrhage Ngo Minh Triet, MD Department of Neurology, University of Medicine and Pharmacy Introduction    Intracerebral hemorrhage (ICH) results from the rupture of an intracerebral vessel 10-35% percent of all strokes (in USA) Its incidence has remained stable over the past three decades despite improvements in primary prevention measures  ICH can result from a number of mechanisms, the predominant one being hypertension  Although lowering the blood pressure in acute hemorrhage holds the theoretical promise of preventing enlargement of the hematoma, many researchers have worried that perihematomal ischemia may be worsened  Evidence now suggests that this concern is a moot point Neuroscience of Cerebral Hemorrhage  Experimental laboratory data in dogs first showed that lowering mean arterial pressure (MAP) within normal limits of cerebral autoregulation did not detrimentally affect regional cerebral blood flow or intracranial pressure (ICP).(Qureshi AI, Wilson DA, Hanley DF, et al Pharmacologic reduction of mean arterial pressure does not adversely affect regional cerebral blood flow and intracranial pressure in experimental intracerebral hemorrhage Crit Care Med 1999;27(5):965–71.)  Positron emission tomography (PET) also fails to demonstrate tissue hypoxia surrounding cerebral hematomas in humans (Hirano T, Read SJ, Abbott DF, et al No evidence of hypoxic tissue on 18F-fluoromisonidazole PET after intracerebral hemorrhage Neurology 1999;53(9):2179–82.)  Powers et al performed a controlled trial of blood pressure reduction in acute patients with ICH and measured perihematomal and global cerebral blood flow; neither declined (Powers WJ, Zazulia AR, Videen TO, et al Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage Neurology 2001;57(1):18–24.)  One study of 118 ICH patients found that 22.9% had positive diffusion signal reflecting acute ischemia during the first month after ICH  The overwhelming majority of these diffusion changes were small and asymptomatic, though blood pressure lowering was associated with these abnormalities (Prabhakaran S, Gupta R, Ouyang B, et al Acute brain infarcts after spontaneous intracerebral hemorrhage: a diffusionweighted imaging study Stroke 2010;41(1):89–94.)  The pilot Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT) was carried out primarily in China and demonstrated that blood pressure could be lowered in the acute setting with relative safety in comparison with a control group (Anderson CS, Huang Y, Wang JG, et al Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial Lancet Neurol 2008;7(5):391–9.) INTERACT2  Randomized 2839 patients, 68% from China, who had a primary ICH within hours of randomization  The intensive treatment arm (goal SBP < 140 mmHg) had a 3.6% decreased chance of death or disability (52% vs 55.6%) compared with the guideline concordant treatment arm (goal SBP< 180 mmHg) (P=0.06)  The ordinal analysis showed significantly lower modified Rankin scores with intensive treatment (P=0.04)  The pivotal INTERACT2 trial demonstrated safety and a trend to improved outcome (Anderson CS, Heeley E, Huang Y, et al Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage N Englb J Med 2013;368(25):2355–65.) Systolic blood pressure levels at and after randomization INTERACT2 Distribution of scores on the modified Rankin scale at 90 days INTERACT2 ATACH  Randomized 1000 patients with intracerebral hemorrhage, intravenous nicardipine to lower blood pressure was administered within 4.5 hours after symptom onset  The primary outcome of death or disability was observed in 38.7% of the participants (186 of 481) in the intensive-treatment group and in 37.7% (181 of 480) in the standard-treatment group (not significant)  The treatment of participants with intracerebral hemorrhage to achieve a target systolicblood pressure of 110 to 139 mm Hg did not result in a lower rate of death or disability than standard reduction to a target of 140 to 179 mm Hg (Qureshi A.I., Palesch Y.Y., Barsan W.G., et al Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage N Engl J Med 2016; 375:1033-1043.) Mean Hourly Minimum Systolic Blood Pressure during the First 24 Hours after Randomization Primary, Secondary, and Safety Outcomes, According to Treatment Group Distribution of scores on the modified Rankin scale at 90 days Choice of antihypertensive agent  Intravenous labetalol or nicardipine may provide smooth onset of action and allow physicians to control blood pressure in patients without cardiac contraindications to these agents  Nitrates theoretically may worsen cerebral edema owing to their vasodilatory properties and should probably be avoided, given the other available agents  Nicardipine infusions are begun at mg/hour The dose can be increased by 2.5 mg/hour every 10 minutes if needed The maximum dose is 15 mg/hour Conclusion  It appears that acutely lowering SBP to a target of 140 mmHg is probably safe if the initial SBP is ≤ 220 mmHg  Current American Heart Association/American Stroke Association guidelines indicate that a target SBP of 140 mm Hg can be effective for improving functional outcome (Class IIa; Level of Evidence B) Xin chân thành cám ơn ý quí đồng nghiệp ... Barsan W.G., et al Intensive Blood- Pressure Lowering in Patients with Acute Cerebral Hemorrhage N Engl J Med 2016; 375:1033-1043.) Mean Hourly Minimum Systolic Blood Pressure during the First 24... et al Rapid blood- pressure lowering in patients with acute intracerebral hemorrhage N Englb J Med 2013;368(25):2355–65.) Systolic blood pressure levels at and after randomization INTERACT2 Distribution... the modified Rankin scale at 90 days INTERACT2 ATACH  Randomized 1000 patients with intracerebral hemorrhage, intravenous nicardipine to lower blood pressure was administered within 4.5 hours after