Background
Every year subarachnoid haemorrhage, a type of stroke caused by bleeding into the space surrounding the brain, affects up to nine people per 100,000 population. Mortality (death) of subarachnoid haemorrhage is 30% to 45%, and 20% of survivors are left dependent in activities of daily living. Currently, short-term treatment may involve changing blood pressure and either inducing hypertension (that is, increasing blood pressure), or lowering blood pressure; however, the beneficial and harmful effects of blood pressure alteration in people with acute subarachnoid haemorrhage are unclear.
Review question
Our aim was to assess the beneficial and harmful effects of altering blood pressure in people with acute subarachnoid haemorrhage.
Search date
We searched scientific databases from their inception to September 2020.
Study characteristics
We identified three randomised clinical trials (studies where people are randomly put into one of two or more treatment groups) assessing blood pressure alterations in people with acute subarachnoid haemorrhage. Two randomised clinical trials enrolling 61 participants compared induced hypertension with placebo (a pretend treatment) or no treatment. One randomised clinical trial enrolling 224 participants compared lowered blood pressure with placebo. We used trial sequential analysis to estimate the number of participants (amount of information) needed to reject or detect important treatment effects. Trial sequential analysis showed that there was a lack of information for all outcomes. All trials were at high risk of bias and we were very unsure about the results.
Key results and conclusion
Our review shows that there is a lack of information about the important treatment effects of induced hypertension or lowered blood pressure in people with acute subarachnoid haemorrhage. Therefore, the beneficial and harmful effects could not be thoroughly assessed. There is an urgent need for randomised trials assessing the effects of altering blood pressure in people with acute subarachnoid haemorrhage, reporting on patient-important outcomes such as mortality, serious side effects, rebleeding, delayed cerebral ischaemia (reduced blood flow to the brain), quality of life, and hydrocephalus.
Based on the current evidence, there is a lack of information needed to confirm or reject minimally important intervention effects on patient-important outcomes for both induced hypertension and lowered blood pressure. There is an urgent need for trials assessing the effects of altering blood pressure in people with acute subarachnoid haemorrhage. Such trials should use the SPIRIT statement for their design and the CONSORT statement for their reporting. Moreover, such trials should use methods allowing for blinded altering of blood pressure and report on patient-important outcomes such as mortality, rebleeding, delayed cerebral ischaemia, quality of life, hydrocephalus, and serious adverse events.
Subarachnoid haemorrhage has an incidence of up to nine per 100,000 person-years. It carries a mortality of 30% to 45% and leaves 20% dependent in activities of daily living. The major causes of death or disability after the haemorrhage are delayed cerebral ischaemia and rebleeding. Interventions aimed at lowering blood pressure may reduce the risk of rebleeding, while the induction of hypertension may reduce the risk of delayed cerebral ischaemia. Despite the fact that medical alteration of blood pressure has been clinical practice for more than three decades, no previous systematic reviews have assessed the beneficial and harmful effects of altering blood pressure (induced hypertension or lowered blood pressure) in people with acute subarachnoid haemorrhage.
To assess the beneficial and harmful effects of altering arterial blood pressure (induced hypertension or lowered blood pressure) in people with acute subarachnoid haemorrhage.
We searched the following from inception to 8 September 2020 (Chinese databases to 27 January 2019): Cochrane Stroke Group Trials register; CENTRAL; MEDLINE; Embase; five other databases, and five trial registries. We screened reference lists of review articles and relevant randomised clinical trials.
Randomised clinical trials assessing the effects of inducing hypertension or lowering blood pressure in people with acute subarachnoid haemorrhage. We included trials irrespective of publication type, status, date, and language.
Two review authors independently extracted data. We assessed the risk of bias of all included trials to control for the risk of systematic errors. We performed trial sequential analysis to control for the risks of random errors. We also applied GRADE. Our primary outcomes were death from all causes and death or dependency. Our secondary outcomes were serious adverse events, quality of life, rebleeding, delayed cerebral ischaemia, and hydrocephalus. We assessed all outcomes closest to three months' follow-up (primary point of interest) and maximum follow-up.
We included three trials: two trials randomising 61 participants to induced hypertension versus no intervention, and one trial randomising 224 participants to lowered blood pressure versus placebo. All trials were at high risk of bias. The certainty of the evidence was very low for all outcomes.
Induced hypertension versus control
Two trials randomised participants to induced hypertension versus no intervention. Meta-analysis showed no evidence of a difference between induced hypertension versus no intervention on death from all causes (risk ratio (RR) 1.60, 95% confidence interval (CI) 0.57 to 4.42; P = 0.38; I2 = 0%; 2 trials, 61 participants; very low-certainty evidence). Trial sequential analyses showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more.
Meta-analysis showed no evidence of a difference between induced hypertension versus no intervention on death or dependency (RR 1.29, 95% CI 0.78 to 2.13; P = 0.33; I2 = 0%; 2 trials, 61 participants; very low-certainty evidence). Trial sequential analyses showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more.
Meta-analysis showed no evidence of a difference between induced hypertension and control on serious adverse events (RR 2.24, 95% CI 1.01 to 4.99; P = 0.05; I2 = 0%; 2 trials, 61 participants; very low-certainty evidence). Trial sequential analysis showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more.
One trial (41 participants) reported quality of life using the Stroke Specific Quality of Life Scale. The induced hypertension group had a median of 47 points (interquartile range 35 to 55) and the no-intervention group had a median of 49 points (interquartile range 35 to 55). The certainty of evidence was very low.
One trial (41 participants) reported rebleeding. Fisher's exact test (P = 1.0) showed no evidence of a difference between induced hypertension and no intervention on rebleeding. The certainty of evidence was very low. Trial sequential analysis showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more.
One trial (20 participants) reported delayed cerebral ischaemia. Fisher's exact test (P = 1.0) showed no evidence of a difference between induced hypertension and no intervention on delayed cerebral ischaemia. The certainty of the evidence was very low. Trial sequential analysis showed that we had insufficient information to confirm or reject our predefined relative risk reduction of 20% or more.
None of the trials randomising participants to induced hypertension versus no intervention reported on hydrocephalus. No subgroup analyses could be conducted for trials randomising participants to induced hypertension versus no intervention.
Lowered blood pressure versus control
One trial randomised 224 participants to lowered blood pressure versus placebo. The trial only reported on death from all causes. Fisher's exact test (P = 0.058) showed no evidence of a difference between lowered blood pressure versus placebo on death from all causes. The certainty of evidence was very low.