Keywords
stroke - thrombectomy - telemedicine - thrombolysis - prehospital - ambulance - neurological
emergencies
Background
A blocked artery in the brain can often lead to irreversible cell death resulting
in an ischemic stroke with major disability or death.[1]
[2] Permanent damage to brain tissue (infarct core) occurs within minutes, with adjacent
regions consisting of areas of brain where blood flow and oxygen are compromised (ischemic
penumbra), but still salvageable. Timely reperfusion of this penumbra is the mainstay
of a “time-is-brain” approach for treating such strokes, with the ultimate goal of
treatment consisting of faster and complete restoration of blood flow of occluded
arteries to save brain cells from irreparable injury.
The standard treatment for acute ischemic stroke involves the administration of intravenous
tissue plasminogen activator (IV tPA) within 4.5 hours of symptom onset, and/or with
intra-arterial mechanical thrombectomy for selected patients with large vessel arterial
occlusions.[3] Not only is earlier recanalization associated with improved outcomes[4]
[5]
[6]
[7]
[8]
[9]
[10] but there is a 15% incremental decrease in chances of a good clinical outcome for
every 30-minute reperfusion delay with intra-arterial treatment.[10]
Despite the potential for IV tPA to improve outcomes for patients with ischemic strokes,
however, only a limited number of patients are able to receive such treatment in a
timely manner.[11]
[12] While reasons for this discrepancy are complex, major obstacles include time delays
in patients' arrival to hospitals capable of administering such treatment.[13]
[14] In some estimates, the median door to needle time in stroke center emergency rooms
in the United States is approximately 60 minutes,[15] with most patients being treated beyond 2 hours.[16] Given the direct relationship of improved outcomes with faster treatment times with
IV tPA,[4]
[5]
[6]
[7]
[8]
[9] minimizing delays in the triage, evaluation, and treatment of patients is vital.
Hospital notification by emergency medical system (EMS) units prior to hospital arrival
is key to faster triage and treatment of stroke patients, leading to more efficient
mobilization of medical teams and initiation of hospital procedures.[17] Administrative delays in the triage process of stroke patients in the emergency
room often offset this potential time savings, however, irrespective of the time needed
to conduct a history and physical, obtain a computed tomography (CT) scan, and initiate
treatment with IV tPA.
Considering the association between faster tPA administration (within the first 60
minutes after symptom onset, the “golden hour”) and a higher frequency of discharge
home (rather than to a nursing facility or other institutions[18]) and better outcomes at discharge,[19] optimization of stroke care is imperative. The use of specially equipped ambulances
in the prehospital setting is one way to facilitate the earlier treatment of stroke
patients. While studies have reported the feasibility of telestroke assessment in
ambulances with regard to various time metrics related to thrombolysis and triage,[20]
[21] evidence to support the impact on clinical outcomes and health care cost savings
has been lacking.
The Mobile Stroke Unit Concept
The Mobile Stroke Unit Concept
Fassbender et al in Homburg, Germany, first proposed[22] and performed[23] the Mobile Stroke Unit (MSU) concept (ambulance equipped with a CT scanner, laboratory
testing, telemedicine [TM] connection to the hospital, and appropriate medication
on-board [OB] the MSU) enabling the prehospital diagnosis and treatment of stroke
in a relatively rural setting. Results from their study demonstrated that prehospital
management achieved a median symptom onset-to-therapy decision time of 56 minutes
(vs. 104 for hospital-based intervention, p < 0.0001) and a median symptom onset-to-treatment time of 72 minutes (vs. 153, p = 0.0011) without any concerns of safety resulting from the use of a MSU. More than
50% of patients had a time-to-therapy decision within the first “golden hour” from
stroke symptom onset.[24]
Similar trends in safety and time savings (time from initial call to treatment) were
seen in the Pre-Hospital Acute Neurological Treatment and Optimization of Medical
care in Stroke (PHANTOM-S) study undertaken in an urban environment by the Stroke
Emergency Mobile Unit (STEMO) group in Berlin, Germany[25] with an increased likelihood for discharge home for patients who received thrombolysis
within the first 60 minutes from stroke onset.[18] An observational, registry-based comparison of 3-month functional outcomes using
modified Rankin scale (mRS) scores suggested a beneficial effect of prehospital thrombolysis
using the MSU, compared with standard hospital-based administration of tPA (odds ratio
[OR]: 1.40, 95% confidence interval [CI]: 1.00–1.97; p = 0.052 for mRS ≤ 1), with a time saving of ∼30 minutes to the initiation of thrombolysis.[26] The STEMO group is currently conducting a prospective study employing a city-wide
coverage scheme consisting of several MSUs working in conjunction with local EMS services
of the fire department.
Following the successes of establishing and operating the first MSUs in Germany, the
earlier treatment of ischemic strokes became a reality in the United States with the
launch of the first MSU in Houston, TX, in May 2014.[27] Following the initial “run-in” phase,[28] the reliability of a TM-based vascular neurologist (VN) to determine tPA eligibility
compared with an OB neurologist was established,[29] along with demonstrable radiation safety of operating a portable CT scanner (radiation
levels were also found to be within normal limits in the MSUs in Germany).[30] A prospective, multicenter, cluster-randomized comparative effectiveness trial (Benefits
of Stroke Treatment Delivered Using a MSU compared with standard management by emergency
medical services) is currently ongoing, which is expected to answer relevant questions
regarding clinical benefit and cost effectiveness, including poststroke health care
utilization and fixed costs of introducing and operating an MSU.[31] The initial establishment in Houston was followed by the implementation of similar
MSU programs across various other sites including Cleveland, Denver, Memphis, Toledo,
New York City, New Jersey, Pennsylvania, Phoenix, Chicago, Los Angeles, and Indianapolis,
with plans to launch similar programs globally in cities such as Paris (France), Edmonton
(Alberta, Canada), and Melbourne (Australia).
The Nuts and Bolts of Setting Up a Mobile Stroke Unit
The Nuts and Bolts of Setting Up a Mobile Stroke Unit
The MSU itself is a standard ambulance that is fitted with a portable CT scanner,
and consists of all necessary equipment needed for the acute evaluation and treatment
of a stroke patient. The MSU team can be composed of either an OB- or TM-based VN,
a nurse skilled in stroke management, a paramedic, and a CT technologist. While the
first prehospital thrombolysis projects relied on physician-staffed ambulances,[23]
[25]
[27]
[28] the group in Cleveland showed that a model using solely a TM VN on a MSU is feasible
and associated with a low technical failure rate (all technical delays were <1 minute
without affecting patient care). The replacement of an OB VN with a TM VN might not
only lead to savings in personnel costs but could also facilitate the simultaneous
operation of multiple MSUs by a single TM VN in geographically distinct areas.[21] Subsequently, the Houston team demonstrated the reliability between an OB VN and
a TM VN in making clinical decisions regarding to tPA eligibility,[29] which was demonstrably comparable to two VNs seeing the same patient in an emergency
department.[32] Time-to-tPA decision (OB: 18 minutes [interquartile range, IQR: 14–23] vs. TM: 21
minutes [IQR: 16–26], p = 0.05) and initiation of tPA bolus were equivalent (OB: 23 minutes [IQR: 19–30]
vs. TM: 24 minutes [IQR: 19–28]), p = 0.70, with 95% CI (−2.18 to 3.24) between an OB VN and a TM-based VN on the MSU.
One of the main considerations in the design of a MSU is the configuration and placement
of the CT scanner. Portable CT scanners (CereTom, NeuroLogica–Samsung Corporation,
Danvers, MA; Somatom Scope, Siemens, Erlangen, Germany) can be installed across the
back wall of the MSU, with special brackets to lock the CT scanner in place during
transport. Depending on the type of CT scanner and space allocation, additional enhancements
are generally necessary to make the power and charging circuitry more robust, including
an upgrade to the standard OB generator to provide additional power for operating
the CT scanner. Eligible patients for tPA are positioned on a gurney which is then
raised to align the patient's head with the scanner when performing the CT scan. A
standard 8-slice, 5-mm configuration is obtained for each patient and is available
for immediate viewing on a portable laptop by the OB VN or readily transmittable to
the TM VN and destination hospital via a cloud-based picture archiving and communication
system.[27] Direct comparison of CereTom images with those from a standard clinical CT scan
have shown a high comparability of CereTom images in terms of diagnostic accuracy
and reliability versus a standard clinical CT scanner.[33] To safeguard radiation exposure and ensure certainty of obtaining quality CT images,
the MSU requires staffing a CT technologist. As a cost-saving measure, CT technologists
can be cross-trained as emergency medical technicians to assist the MSU paramedic/nurse
when an OB VN is not available and/or can become also highly skilled in other forms
of imaging modalities. Essential point-of-care testing, including fingerstick glucose,
international normalized ratio, and creatinine, is readily obtainable and accessible
on the MSU, without causing any treatment delays.
Establishing MSUs can be a challenging venture and requires prudent financial investment.
The ideal structure and operational design of the MSU will depend on regional/local
terrains, bureaucratic regulations, as well as available economic resources.[27] Monetary costs to build and fully equip a functional MSU are estimated to be between
$600,000 and $2 million. Although currently available cost-effectiveness studies suggest
that the expenditure pays off in the long run,[34]
[35] the predictive utility is limited. It is anticipated that future research will provide
more robust cost-effectiveness analyses.[28]
[31]
Applications beyond Tissue Plasminogen Activator
Applications beyond Tissue Plasminogen Activator
Although reducing time to thrombolysis is a key goal of MSUs, the potential benefits
of earlier assessment and MSU intervention are far more expansive. Given recent evidence
from clinical trials showing the efficacy of endovascular therapies (ETs) for large
vessel strokes,[36]
[37]
[38] it is vital for triage processes in stroke care to be modified in a manner that
promotes efficient triage of ET-eligible patients directly to stroke centers with
ET capability. Considering the reduced probability of intra-arterial treatment for
every minute of transfer delay to an ET capable hospital,[39] the identification of patients with large vessel occlusions and/or salvageable penumbra
using CT angiography and perfusion on the MSU can save time in the field by bypassing
initial transport to non-ET facilities, expedite laboratory testing by using point-of-care
testing,[40] facilitate faster administration of IV tPA, and shorten times to intra-arterial
therapy.[41] The benefits of MSU triage are not only applicable to patients needing ET but are
also applicable to virtually any ischemic stroke patient who can benefit from care
in hospitals with dedicated stroke units and patients with intracerebral hemorrhages
(ICHs) to centers with neurosurgical expertise.[42] Beyond stroke, efficiency in prehospital triage may also be helpful in patients
with head trauma[43] and other acute neurological emergencies (i.e., status epilepticus) by having patients
being diverted to hospitals with expertise in neurological emergencies and critical
care. Streamlined triage processes ([Fig. 1]) are thus an integral feature of the MSU paradigm.
Fig. 1 Algorithm of MSU work flow and triage. Cr, creatinine; CSC, comprehensive stroke
center; CT, computed tomography; EMS, emergency medical services; MSU, Mobile Stroke
Unit; OB VN, on-board vascular neurologist; POC, point of care; PSC, primary stroke
center; TM VN, telemedicine vascular neurologist; tPA, tissue plasminogen activator.
MSUs also allow for the rapid management of patients with ICH. Since hemorrhage enlargement
occurs more frequently early in the course of ICH,[44]
[45] the MSU provides an avenue to promptly administer intravenous antihypertensive medications
to control blood pressure and/or other hemostatic agents (i.e., prothrombin complex
concentrate for warfarin-associated hemorrhages) and antidotes for specific agents
(i.e., idarucizumab for dabigatran) to treat coagulopathies that are associated with
ICHs.
MSUs are also an instrumental tool for research spanning broad domains, including
biomarkers,[46]
[47] neuroimaging,[48] and cerebral physiology (via the use of noninvasive cerebral blood flow monitoring
devices).[49] The effects of earlier administration of time-sensitive, adjunctive neuroprotective
therapies with tPA, along with other hemostatic agents for ICH (i.e., tranexamic acid,
factor VIIa) can also be potentially investigated. Dedicated teams, ideally with proficiency
in both clinical care and research, will have an invaluable resource given the unique
opportunities offered by MSUs.
Future Directions
The optimal setting (e.g., rural vs. urban) where MSUs can have maximal impact will
need to account for innumerable factors, including local EMS systems and protocols,
cooperation between hospitals, environmental landscapes, and population dynamics.
In urban settings, the proficiency of MSU operations will likely depend on the success
of integrating the MSUs within EMS response algorithms and the interplay between EMS
responders and hospital systems with differing capabilities of managing stroke patients
(i.e., comprehensive stroke centers vs. primary stroke centers, hospitals with neurosurgery,
and/or neurocritical care expertise). Significant reductions in time to decision can
be made by utilizing a “rendezvous model” in rural settings, where instead of having
to wait for patients to be transported to the closest stroke center (which may be
distant and require prolonged travel times), MSUs can travel out to meet the incoming
ambulance, thereby leading to reductions in time to treatment. This rendezvous approach
can also be applied to urban areas and expand the service areas of these units from
their base of operation.[28] Ultimately, the diagnosis of the patient, stroke severity, patient preference, and
possibly other region/country-specific rules and regulations will dictate the feasibility
of operations of a particular MSU.
One of the keys to the widespread application and success of MSUs will be the standardization
of MSU processes and operations across the world. The Prehospital Stroke Treatment
Organization (PRESTO) was thus organized in 2016 as a collaboration of international
medical providers to improve patient outcomes and promote research across the various
spheres of stroke care in the prehospital setting. By facilitating the expansion of
MSU programs worldwide, PRESTO can establish a global and cohesive network of stroke
care that can link patients, public/municipal resources, and providers alike. On a
worldwide scale, MSUs hold great promise with the potential to improve patient outcomes
and provide more cost-effective medical care.[50]
