The Masterstroke trial

The Masterstroke trial

 

Management of systolic blood pressure during thrombectomy by endovascular route for acute ischaemic stroke: the MASTERSTROKE trial

Stroke is the third highest cause of mortality in Australia and costs the economy $5 billion per year. 

Project summary

In addition, survivors of stroke are left with lifelong disability with consequent emotional and financial burdens on patients, carers, and health care providers. The most severe form of ischaemic stroke occurs with large vessel occlusion (LVO). Australia and New Zealand is at the forefront of introducing a new therapy, endovascular thrombectomy (EVT) with recanalization rates as high as 88 per cent and performing 53 procedures per million population in 2018. The effectiveness of EVT for the treatment of acute ischaemic stroke caused by LVO has been demonstrated in randomised controlled trials. However, peri-procedural factors such as relative hypotension have been shown to worsen outcomes. Acute ischaemic stroke is known to impair cerebral autoregulation, which is a protective mechanism thought to preserve cerebral blood flow (CBF) over a wide range of systemic blood pressures (BP). Many patients have general anaesthesia (GA) for EVT. Common agents used to maintain GA such as propofol, sevoflurane and desflurane are known to impair cerebral autoregulation in a dose dependent fashion.
 
In rat models, our data show that propofol and sevoflurane ablate cerebral autoregulation in the ischaemic territory during middle cerebral artery occlusion. This means that global CBF and blood flow in ischaemic territories during stroke become dependent on BP during GA. Impaired cerebral autoregulation (from ischaemia and anaesthetic drugs) means these effects may make any periods of relative hypotension especially harmful leading to reduced penumbral blood flow, increased infarct size and poorer outcome.
Many centres globally choose to perform EVT under local anaesthesia (LA) or conscious sedation (CS).
 
Observational data comparing GA with CS, and non-randomised comparisons of GA with CS from clinical trials suggest GA confers worse outcomes. However, BP data was often not reported in these studies, allowing the possibility that confounding by differential BP management, rather than the effects of GA per se causes poorer functional outcomes. Conversely, in randomised controlled trials comparing GA with CS, where BP management was reported and was comparable between groups, clinical outcomes were either equivalent or superior with GA. Meta-analyses of these trials showed statistically significant improvement in functional independence (number needed to treat of 8) at 3 months in the GA group.
 
Reasons why GA may be advantageous in EVT are unknown but may include improved procedural and imaging conditions and also reduction of intra-procedural complications. GA may also have neuroprotective effects as both propofol and sevoflurane reduce cerebral metabolic rate (CMRO2), which may potentially benefit the cerebral penumbra by reducing metabolic demand until reperfusion.
 
EVT is a highly effective therapy. Any further therapeutic improvements will reduce disability, improve quality of life and reduce long-term healthcare costs. The intervention tested in this study adds no additional healthcare costs and would be immediately available to all patients having EVT under GA. Current data suggests improved procedural and 3-month functional outcomes from having GA, hence we anticipate any findings to be immediately implementable for EVT in Australia and New Zealand.
For all the latest updates on the MASTERSTROKE Trial, follow @MASTERSTROKE_nz on Twitter.

Chief investigators

Dr Doug Campbell, Dr Carolyn Deng, Dr Robyn Billing, Professor Tim Short, Professor Alan Barber, Auckland City Hospital, New Zealand, Dr David Highton, Princess Alexandra Hospital, Queenslan

Funding

The project was awarded $A69,560 through the ANZCA research grants program for 2022.   

Trial registration

Australian New Zealand Clinical Trials Registry registration number: ACTRN12619001274167

For more information

For further information about this study, please contact the MASTERSTROKE principal investigator, Dr Doug Campbell by email.

Last updated 12:08 16.11.2022