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Page 6 of 12 Zhao et al. Vessel Plus 2021;5:10 I http://dx.doi.org/10.20517/2574-1209.2020.77
savings from faster thrombolysis on the MSU would have avoided 20.9 disability-adjusted life years, and
[2]
24.6 disability-adjusted life years for faster EVT . This suggests that despite the smaller number of cases,
the more powerful effects of EVT compared to thrombolysis meant that faster EVT is the more clinically
impactful advantage conferred by the MSU.

This is also predicated on a linear assumption of outcome decay with time, which is likely not true as the
benefits for reperfusion therapy decrease fastest in the early timepoints [23,26] . Given the data on the dramatic
improvement in golden hour thrombolysis, the early timepoints are clearly where the Melbourne MSU is
having an impact, meaning our disability avoidance estimates may be conservative.

Benefits for hemorrhagic stroke
Whilst the MSU platform was conceived primarily for treatment of ischemic stroke, triage and pre-hospital
treatment also benefits patients with intracranial hemorrhage. Of all hemorrhage patients attended to by
the MSU in the first 365 operational days, 28% received a CT scan within 60 min of symptom onset and
60% within 90 min. In contrast, 15% and 47% of ischemic stroke patients received thrombolysis within 60
and 90 min respectively on the MSU. This suggests that MSUs can intervene in intracranial hemorrhage
at a similarly fast time window as ischemic stroke, which is critical as hematoma growth is highly time-
[27]
dependent . In addition, our data also show that almost half of all hemorrhage patients (48%) have proven
or suspected hematoma growth (suspected cases are those who clinically deteriorated). This figure is
substantially higher than the placebo arms of past hemostatic trials [28-30] , likely due to the earlier assessment
and imaging enabled by the MSU. MSUs therefore have the unique role in providing ultra-early therapies in
intracranial hemorrhage and determining their potential role in functional outcomes.

Although effective treatments are much more limited for parenchymal intracerebral hemorrhage, a post-
hoc analysis of a major trial of aggressive blood pressure management in intracerebral hemorrhage
[31]
demonstrated improved outcomes if anti-hypertensive therapy is initiated within 2 h of symptom onset .
In the first 365 days, 42% of MSU hemorrhage patients required acute intravenous anti-hypertensive
therapy, which would be delayed if patients received standard ambulance transport. Pre-hospital imaging
and management by the MSU therefore allows faster treatment for blood pressure and potentially greater
stabilization of hematoma growth.

The other major therapy provided by the MSU is reversal of anti-coagulation associated hemorrhage. The
Melbourne MSU provides reversal for patients on therapeutic warfarin using intravenous vitamin K and
3-factor prothrombin concentrate (6% of all intracerebral hemorrhage in the first 365 days, n = 3) and also
for dabigatran-associated hemorrhage with intravenous idarucizumab. Although specific reversal therapy
[32]
for rivaroxaban and apixaban exists in the form of andexanet-alpha , this is not yet available for use in
Australia. The MSU again has substantial advantages in providing earlier treatment, as there is preliminary
[33]
evidence that delayed warfarin reversal is associated with poorer outcomes .
Similar to large vessel occlusion, pre-hospital diagnosis of intracranial hemorrhage by the MSU allowed
improved triage of patients directed to a comprehensive center with neurosurgical units. Our data shows
around a quarter of all hemorrhage patients bypassed their local hospital, some of which subsequently
underwent emergent neurosurgical intervention. This treatment would have been severely delayed had
patients needed a secondary inter-hospital transfer, as transfer processes are even slower than for EVT in
Melbourne due to the absence of an established protocol. Such delays are likely to be especially deleterious
to younger patients with rapidly progressive hemorrhages, where earlier neurosurgical intervention
may delay, reduce, or even prevent disability. Even if patients did not receive surgical intervention, high
risk cases require management at a neurosurgical center for neuro-critical care monitoring, especially