A Comprehensive Study On The Management Of Blood Pressure In Patients With Acute Severe Stroke

?Background?A stroke is a medical emergency in which poor blood supply caused by craniocervical vascular occlusion or rupture to the brain results in focal or diffuse neurological dysfunction.With a very high mortality and morbidity,stroke is the second leading cause of death around the world.Severe stroke is a life-threatening cerebral vascular event which causes major neurological function deficits and leads to multiple organ dysfunctions,such as respiratory and circulatory failure.Patients with severe stroke are usually in a critical condition with many complications and are more likely to develop neurological deterioration,accordingly an intensive care for monitoring and treatment is necessary and crucial.Elevated blood pressure(BP)is one of the most common clinical manifestations in acute stroke,and it happens in more than 75% of stroke patients.In patients with severe stroke,58% to 81% of them have a history of hypertension.Therefore,the management of BP plays a fundamental and essential part in medical care of acute severe stroke.High BP may cause deterioration of cerebral edema,hemorrhagic transformation of infarction,cardiac complication,renal dysfunction,and many other serious conditions,whereas lower BP level can reduce blood perfusion in multiple organs,especially in the brain,and exacerbate cerebral injury.The management of BP in acute stroke has been a research hotspot for many years.However,the conclusions of these large clinical trials were conflicting,some supported BP lowering treatments,some opposed BP lowering treatments,and some had neutral results.Moreover,the whole populations or the majority of the populations included in those large multicenter randomized controlled trials(RCTs)were not patients with severe stroke.Guidelines for the management of severe stroke also made no recommendations on the optimal BP lowering goals due to a paucity of data from high quality clinical trials.?Objectives?1.To investigate the associations between different ranges of BP and functional outcome in acute severe stroke and provide theoretical proofs for the further design of a prospective,multicenter,randomized trial on the management of elevated BP in acute severe stroke.2.To determine the therapeutic benefit and safety of individualized BP lowering treatment(10–15% reduction from admission level)compared with guideline-recommended BP lowering treatment(acute ischemic stroke [AIS]: systolic blood pressure [SBP] ? 200 mmHg;intracerebral hemorrhage [ICH]: SBP ? 180 mmHg)in acute severe stroke.3.To investigate the characteristics of BP fluctuation in patients with acute severe stroke,and examine the associations between BP variability and functional outcome.?Methods?1.From September 2012 to September 2016,all consecutive patients with acute stroke admitted to neuro-intensive care unit of Xijing hospital were respectively included in this study.The associations between SBP / diastolic blood pressure(DBP)on admission and functional outcome at hospital discharge were analyzed.The rate of SBP change within 24 after admission was calculated,and the mortality and major disability rates were compared between patients with different rates of SBP change.Modified Rankin scale score(mRS)was used to evaluated the functional outcomes in severe stroke.2.We conducted a prospective,randomized,multicenter study,Controlling Hypertension After Severe Cerebrovascular Event(CHASE)trial,in the first affiliated hospital of Air Force Medical University and other 25 district general hospitals in Shaanxi province.Five hundred eligible patients were randomized into individualized BP lowering group(with 10–15% reduction in systolic blood pressure [SBP] from admission level)or guideline-recommended BP lowering group(with a target SBP of <200 mm Hg in AIS and <180 mm Hg in ICH).The primary outcome was the proportion of patients with a poor outcome(unable to live independently or all-cause death,defined as a mRS score of 3 – 6)at day 90 of enrollment.Secondary outcomes included poor outcome and major morbidity at hospital discharge and the ability of activities of daily living at day 90 of enrollment.3.We conducted a post-hoc analysis with data from CHASE trial.The BP variability in the acute phase(in the first 24 hours after enrollment)and in the subacute phase(over days 2 – 7 after enrollment)were studied.Standard deviation(SD)of BP was chosen as the key parameter for BP variability.Mean,maximum,minimum,coefficient of variation(CV),successive variation(SV),and average real variability(ARV)were also calculated and analyzed.Associations between BP variability and functional outcome were estimated using three logistic regression models.?Results?1.A total of 302 patients with acute severe stroke were included in the study.A V-shaped pattern between baseline SBP and the rate of severe poor outcome(mRS: 5-6)at hospital discharge was observed.A basin-shaped pattern between baseline SBP,DBP,and mRS scores at hospital discharge was observed,and patients with BP of 120-140/70-80 mmHg on admission had the best functional outcome.Both high and low BP were associated with poor outcome in patients with acute severe stroke.In-hospital mortality was significantly higher in patients with SBP reduced by > 15% within 24 hours from baseline than those with SBP reduced by ? 15%(P = 0.016).2.From January 2017 through August 2018,a total of 16029 patients were screened in 26 district general hospitals,of whom 500 patients underwent randomization.After exclusion of 17 subjects who withdrew consent or were ineligible examined by quality control,243 in individualized BP-lowering group and 240 in guideline-recommended BP-lowering group were included in the final analysis.Participants who were assigned to receive individualized BP-lowering treatment had an absolute reduction of 2.3% in the rate of three-month poor outcome compared with participants who were assigned to receive guideline-recommended BP-lowering treatment,but the effects of two treatments were not significantly different(odds ratio with individualized treatment,0.75;95% confidence interval,0.47 to 1.19;P = 0.222).The generalized linear analysis showed that the individualized treatment had a significant effect on reducing the neurological deficits at hospital discharge evaluated by NIHSS(beta estimate,-0.13;95% CI,-0.2 to-0.03;P = 0.009),compared to guideline-recommended treatment.In other secondary outcomes,no significant difference of effects between the two treatments were observed.The rates of serious adverse events within 90 days and 90-day mortality in the two groups were similar.3.No association between SBP variability(mean,maximal,minimal,SD,CV,ARV)during the first 24 hours after admission and three-month poor outcome was observed in patients with severe stroke.SBP variability over days 2 – 7 after admission was independently associated with three-month poor outcome.The three-month mortality increased as SD of SBP over days 2 – 7 increased.No association between DBP variability during the first 24 hours after admission and three-month poor outcome was observed,but DBP variability over days 2 – 7 was also found to be independently associated with three-month poor outcome.?Conclusions?1.Both high and low BP led to a higher rate of poor outcome in patients with acute severe stroke.A reduction of more than 15% from baseline in SBP may induce higher rates of mortality and morbidity.2.In patients with acute severe stoke,individualized BP lowering treatment did not significantly reduce the rate of three-month death or severe disability.Acute lowering of SBP to 10% to 15% reduction from baseline is safe in patients with severe stroke and may be effective for reducing neurological deficits at hospital discharge.3.For patients with acute severe stroke,it's necessary to reduce dramatic BP fluctuation and maintain BP stable during the subacute phase.Especially for patients with AIS,it's crucial to avoid a very low BP level.