Question
We wanted to compare the effectiveness of haemodilution (diluting the blood) treatment, started within 72 hours of stroke onset, versus control or no treatment in people with ischaemic stroke to assess the impact on death or dependence.
Background
Stroke is the second leading cause of death worldwide. Symptoms of stroke include face drooping, arm weakness and difficulty with speech. Most strokes are caused by a blood clot that interrupts blood flow to a part of the brain. If blood flow is not restored quickly, the brain cells will die. Haemodilution improves the flow properties of the blood so that, theoretically, oxygen and nutrient supply to the brain is improved and brain cells threatened to die could survive. This treatment reduces brain infarct (the area of dead cells) size in animals with experimental stroke. Haemodilution can be achieved by blood-letting (removing blood), by giving fluids as an infusion or by a combination of both. The fluids used may be salt solutions but colloid solutions, which consist of large insoluble molecule meant to retain fluid intravascularly, are more effective as haemodilution agents. In many countries, haemodilution has been used in clinical treatment of people with acute stroke since the 1970s. Since then, a large number of clinical studies on haemodilution in acute stroke have been published. The goal of this review was to determine if blood dilution could prevent death in people with stroke due to blood clots.
Study characteristics
We identified 21 trials involving 4174 adult, male and female participants with presumed acute ischaemic stroke. The evidence is current to February 2014. Many trials followed participants for at least three to six months. Interventions included isovolaemic regimens (replacing a portion of blood volume with fluid) and hypervolaemic regimens (increasing the total volume of blood by adding fluid) using different types of solutions.
Key results
This review showed that, when all the studies are taken together, there is no clear evidence of benefit from haemodilution. There is also no clear evidence that any particular mode of haemodilution, with or without blood-letting, using various types of haemodiluting agents, etc, is beneficial. There were no significant serious side effects of this treatment. It is concluded that there is no clear scientific support for the use of haemodilution in the routine treatment of people with acute ischaemic stroke.
Quality of the evidence
The overall quality of the evidence was moderate as individual trials were of varying quality. There was little variation among trials.
The overall results of this review showed no clear evidence of benefit of haemodilution therapy for acute ischaemic stroke.
These results are compatible with no persuasive beneficial evidence of haemodilution therapy for acute ischaemic stroke. This therapy has not been proven to improve survival or functional outcome.
Ischaemic stroke interrupts the flow of blood to part of the brain. Haemodilution is thought to improve the flow of blood to the affected areas of the brain and thus reduce infarct size.
To assess the effects of haemodilution in acute ischaemic stroke.
We searched the Cochrane Stroke Group Trials Register (February 2014), the Cochrane Central Register of Controlled Trials (Issue 1, 2014), MEDLINE (January 2008 to October 2013) and EMBASE (January 2008 to October 2013). We also searched trials registers, scanned reference lists and contacted authors. For the previous version of the review, the authors contacted manufacturers and investigators in the field.
Randomised trials of haemodilution treatment in people with acute ischaemic stroke. We included only trials in which treatment was started within 72 hours of stroke onset.
Two review authors assessed trial quality and one review author extracted the data.
We included 21 trials involving 4174 participants. Nine trials used a combination of venesection and plasma volume expander. Twelve trials used plasma volume expander alone. The plasma volume expander was plasma alone in one trial, dextran 40 in 12 trials, hydroxyethyl starch (HES) in five trials and albumin in three trials. Two trials tested haemodilution in combination with another therapy. Evaluation was blinded in 14 trials. Five trials probably included some participants with intracerebral haemorrhage. Haemodilution did not significantly reduce deaths within the first four weeks (risk ratio (RR) 1.10; 95% confidence interval (CI) 0.90 to 1.34). Similarly, haemodilution did not influence deaths within three to six months (RR 1.05; 95% CI 0.93 to 1.20), or death and dependency or institutionalisation (RR 0.96; 95% CI 0.85 to 1.07). The results were similar in confounded and unconfounded trials, and in trials of isovolaemic and hypervolaemic haemodilution. No statistically significant benefits were documented for any particular type of haemodiluting agents, but the statistical power to detect effects of HES was weak. Six trials reported venous thromboembolic events. There was a tendency towards reduction in deep venous thrombosis or pulmonary embolism or both at three to six months' follow-up (RR 0.68; 95% CI 0.37 to 1.24). There was no statistically significant increased risk of serious cardiac events among haemodiluted participants.