Swiss guidelines for the prehospital phase in suspected acute stroke

Acute stroke treatment has advanced substantially over the last years. Important milestones constitute intravenous thrombolysis, endovascular therapy (EVT), and treatment of stroke patients in dedicated units (stroke units). At present in Switzerland there are 13 certified stroke units and 10 certified EVT-capable stroke centers. Emerging challenges for the prehospital pathways are that (i) acute stroke treatment remains very time sensitive, (ii) the time window for acute stroke treatment has opened up to 24 h in selected cases, and (iii) EVT is only available in stroke centers. The goal of the current guideline is to standardize the prehospital phase of patients with acute stroke for them to receive the optimal treatment without unnecessary delays. Different prehospital models exist. For patients with large vessel occlusion (LVO), the Drip and Ship model is the most commonly used in Switzerland. This model is challenged by the Mothership model where stroke patients with suspected LVO are directly transferred to the stroke center. This latter model is only effective if there is an accurate triage by paramedics, hence the patient may benefit from the right treatment in the right place, without loss of time. Although the Cincinnati Prehospital Stroke Scale is a well-established scale to detect acute stroke in the prehospital setting, it neglects nonmotor symptoms like visual impairment or severe vertigo. Therefore we suggest “acute occurrence of a focal neurological deficit” as the trigger to enter the acute stroke pathway. For the triage whether a patient has a LVO (yes/no), there are a number of scores published. Accuracy of these scores is borderline. Nevertheless, applying the Rapid Arterial Occlusion Evaluation score or a comparable score to recognize patients with LVO may help to speed up and triage prehospital pathways. Ultimately, the decision of which model to use in which stroke network will depend on local (e.g. geographical) characteristics.


Introduction and methodology
Randomized controlled studies of the last two decades have proven the impressive benefit of acute stroke therapy. This is true for both treatment in a stroke unit 1 and for revascularization procedures such as intravenous thrombolysis (IVT) and endovascular therapy (EVT) of proximal vessel occlusion (large vessel occlusion (LVO)). [2][3][4][5][6] Actually, 70-80% of patients with acute ischemic stroke do not have LVO and are ideal candidates for IVT in the setting of a stroke unit or center. In contrast, the remaining 20-30% of patients with LVO benefit from additional or isolated EVT in a stroke center setting. In the latter category, triage in a non-center hospital can delay the time to open the occluded vessel by up to 100 min. 7,8 Most of the time is lost in the first care hospital for diagnostics and possibly IVT before transfer to the stroke center. For patients without LVO, however, the longer transport to a distant stroke center instead of a nearby stroke unit could delay systemic thrombolysis. Accordingly, both under-and over-triage to a stroke center may be associated with worse outcome.
This knowledge indicates that the emergency medical service plays a crucial role in the appropriate triage of stroke patients. On the one hand, transfer of all stroke patients to a stroke center should be avoided. On the other hand, under-triage to a stroke center of patients with potential indication for EVT should be minimized.
An additional challenge in the prehospital phase is patients with unknown symptom onset, including strokes occurring during sleep ("wake-up stroke" and "siesta stroke"). With advanced imaging available in all stroke units and stroke centers, some of the patients can go on to benefit from IVT up to about 9 h after symptoms onset or last proof of good health (LPGH). 9,10 For EVT in the context of LVO, the time window may be extended to at least 24 h after symptoms onset/LPGH. 11,12 The multidisciplinary working group for "Prehospital phase of stroke" of the Swiss Stroke Society prepared the present recommendations for the prehospital phase of stroke based on the current literature and Swiss conditions. The Swiss Society for Emergency and Rescue Medicine, the Swiss Neurological Society, the Swiss Association of Paramedics, and the Inter Association of Rescue Services coauthored and approved the recommendations. The overall aim is to organize clearly the prehospital phase for stroke in Switzerland so that (i) the vast majority (*90%) of patients with an acute stroke are treated at a stroke unit/stroke center and (ii) transport to a stroke unit or stroke center happens without unnecessary time delays. 144 emergency calls center: Does the patient have a possible acute stroke?
When the emergency services first come into contact with the patient, the fundamental questions they need to resolve are, does the patient have a stroke at all and if yes, how acute is it. This should first be attempted by the 144 emergency calls center and then again by the paramedics on-site.
The 144 emergency call centers in all regions of Switzerland should have a standard checklist, which they can use to determine the level of emergency by checking a list of predefined stroke symptoms (or special signs). An example of such a checklist is shown in Table 1.

Triage 1 on-site: Does the patient have an acute stroke or not?
At first contact with the patient, the paramedics (on-site) should decide quickly if the patient has a stroke or not. At this stage triage with a high sensitivity is important and the Cincinnati Prehospital Stroke Scale (CPSS), for example, is well suited for this purpose. However, this scale only measures motor skills and speech.
We propose for triage 1 therefore, scoring the "acute occurrence of a focal neurological deficit." In addition to motor function and speech, we also include acute severe dizziness and acute visual impairment. The emergency service staff should try to discover when the acute neurological deficit started. If the time of onset of symptoms is unclear, it should be taken as the time of last indication of a normal state of health ("Last Seen Well Time"). If the symptoms occurred in sleep, this is considered "acute." Recommendations for triage 1 -A patient with an acute focal neurological deficit, that is, with symptom onset within the last 24 h or on waking, should be taken to a hospital with a stroke unit or stroke center as soon as possible (with special signal). These capable hospital facilities have neurovascular multimodal imaging (vessel/mismatch) and IVT offered 24 h/7 days. -Nearby hospitals without these infrastructures should be bypassed unless cardiorespiratory instability prevents further travel. -In cases of complete disappearance of all symptoms and clinical signs (transient ischemic attack) or in cases of a clear preexisting severe disability, transport to a stroke unit/stroke center can go ahead in the absence of a special signal. -Difficult situations for triage decisions for the emergency service can be discussed with stroke specialists at the stroke center (SC)/stoke unit (SU).

Triage 2 on-site: Does the patient have a LVO?
In principle, the more severe the stroke, the more likely is an LVO. Since the paramedics usually treat a stroke patient without medical supervision on scene, a paramedic must be able to carry out triage 2 reliably and quickly. The prehospital LVO triage tool should have sufficient sensitivity/ specificity to keep the number of false triages as low as possible. Several scores are under development to determine LVO yes/no as accurately as possible in the prehospital phase. The progress and performance of these scores are discussed in the Online Appendix 1. Although evidence is still lacking concerning triage benefit and the "best" triage score, this working group favors triage using the Rapid Arterial Occlusion Evaluation (RACE) score because of its good discriminatory power and its validation by paramedics already in the prehospital setting. [13][14][15][16] Other tests such as gaze-face-arm-speech-time (G-FAST) may also be used as they are faster and easier, but their discriminatory power seems less good (see Online Annex 1). Of note, it has been described that thrombectomy is also effective for LVO patients with low symptomatology ( If an LVO is likely based on the chosen score, there are different prehospital concepts which will briefly be discussed below.

Drip and Ship concept
A patient with a suspected stroke would be taken to the nearest stroke unit by ambulance if it were closer than the stroke center. If LVO is diagnosed in the unit by imaging (computed tomography [CT]/MRI), the patient is immediately transferred to the nearest stroke center (by ground or air) with ongoing systemic thrombolysis. The stroke center would be alerted, the images transmitted electronically, and the patient transferred directly on arrival to the angio-suite without repeating the diagnosis, provided there is no clinical worsening.
Advantages of this concept are: -Short time to systemic thrombolysis (onset-toneedle) with possible revascularization by IVT alone. -A higher thrombolysis rate.
-Triage LVO versus no LVO very good as based on imaging.
The disadvantages: -The potential loss of time (onset-to-groin puncture) in patients with LVO due to the detour via a stroke unit and organization of further transport.
The following critical time variables should be met: -The time from entry into the first stroke unit to further transport (door-in-to-door-out (DIDO) time) must be kept as short as possible (target: door-to-needle: 30 min, turnaround 20 min ¼ DIDO target < 50 min; max 60 min). -In addition, appropriate organization of the stroke center is necessary to keep the "door-to-groinpuncture time" as low as possible (target: 30 min; max. 60 min). 18

Mothership concept
The core of this concept is that the emergency service drives (or flies) the patient directly to a stroke center if LVO is suspected, even if there is a stroke unit nearby. In the stroke center, the patient is usually thrombolysed after diagnosis and then transferred to the angio-suite for EVT. The data regarding the abovementioned concepts are still insufficient: Two nonrandomized prospective studies showed worse functional outcome for Drip and Ship compared to the Mothership concept. 19,20 On the other hand, two retrospective studies did not find a difference in clinical outcome between the two prehospital concepts. 21,22 A randomized study comparing the Drip and Ship with the Mothership concept for suspected LVO strokes occurring remotely from and endovascular center showed similar 3 months functional outcomes in both arms. 23

Drip and Drive concept
In this concept, a stroke patient living closer to a stroke unit than to a stroke center is examined in the former for LVO. If there is an indication for EVT, a neuroradiologist drives from a stroke center to the stroke unit to perform EVT there rather than transporting the patient.
Advantage of this concept: -A small study measured average time intervals and saw that the time to recanalization was about 2 h shorter than the above Drip and Ship concept. 7 Disadvantage: -The data regarding this concept are not yet convincing and depend strongly on the local situation. -The major problems of the Drip and Drive concept are the human resources certainly as well as the availability of trained personnel on-site.
At present, we consider this solution of little use in Switzerland. Nevertheless, this study does indicate that the Drip and Ship concept results in significant time loss.

Mobile thrombolysis on-site
Here, an ambulance incorporating acute imaging (CT) and IVT procedure drives to the patient with a suspected stroke. Advantage: This allows rapid IVT to be performed on-site if necessary, screening the patient for LVO and direct transport to a stroke center. 24 Disadvantage: This concept requires significant investments in money and human resources, and seems to be particularly useful for densely populated areas with about a million persons or more.
The authors agree that mobile thrombolysis is of unlikely benefit for Switzerland because of relatively small cities and the high density of stroke units and stroke centers and the geographical conditions.

Recommendations for triage 2: Does the patient have a LVO?
A precise statement on whether Drip and Ship or Mothership should be favored is not possible at present. Preliminary results of a large randomized study in Catalonia indicate that both models lead to similar clinical outcomes within a well-organized stroke care system. 23 Some studies have used models to calculate which concept should be favored over another and when. 18,25 The results depend highly on the distance between the event location, stroke unit, and stroke center but also on the capabilities of the particular stroke unit and stroke center. In principle, the current data allow us to make the following assertions (see Table 2): -Patients should be transferred directly to the stroke center if the distance from the event to the stroke center is <20 min. -If the distance to a stroke unit is shorter than to the stroke center, the Drip and Ship concept would make sense with a transport time of >20 min between the two institutions. -Avoid driving away for more than 10 min from the stroke center toward a stroke unit, as this route would have to be taken again to the stroke center if needed (Figure 1).

With the Drip and Ship concept
-Critical time intervals should be measured and analyzed: DIDO time of the stroke unit: target <50 min; max. 60 min. -The incoming emergency team should remain onsite until referral (or not) to an SC. -Imaging should not be repeated at the SC, except in exceptional and justified cases. -In the SC, the goal is to achieve a "door-to-groinpuncture time" of 30 min (max. 60 min).
In the event that there is no prehospital triage for LVO, the Drip and Ship concept critical time-criteria apply ( Figure 2).

Prehospital concepts for specific time windows
If an acute neurological deficit occurs within 24 h, the patient must be triaged for transport to the stroke unit or stroke center. A fast and problem-oriented workup with targeted medication or interventional secondary prophylaxis in a stroke unit/ stroke center reduces the probability of long-term disability even without acute revascularization treatment. 1

Time window <8 h after symptom onset/LPGH or since waking up (wake-up stroke)
In this situation, the nearest thrombolysis-capable facility (stroke unit or stroke center) should be reached with special signal.
If the LVO score is positive (e.g. RACE 5), the above recommendations for triage 2 should be consulted for choosing a stroke unit or stroke center.

Time window 8-24 h after symptom onset/LPGH or since waking up (wake-up stroke)
If the LVO score is positive (e.g. RACE   center ("Mothership") with special signal. If the LVO score is low (e.g. RACE < 5), patients are transported without special signal to the nearest stroke unit or center for clarification and treatment. If there is no triage for LVO, transfer should be performed with special signal to the nearest stroke unit/stroke center. The time indications for onwards transport to the SC apply as to the Drip and Ship concept.

Mode of transport and general measures in the prehospital phase
If a stroke is suspected from an acute neurological deficit, the general Swiss emergency number (144) should be called without delay.
If the estimated time by ground transport from the patient's location to the target hospital is more than 45-60 min, air transport may be faster. The choice of the most appropriate means of transport is the responsibility of the 144 emergency control center and depends on the weather conditions, traffic density, landing possibilities, and availability of transport.
If the patient goes by air (helicopter), the patient should be taken directly to the nearest stroke center, regardless of the severity of the symptoms (RACE score). A stopover in a stroke unit can lead to long delays for LVO, which is counterproductive to the time gained by flying directly to a stroke center.
To improve information flow, the rescue service/air rescue should provide practical preliminary information to the facility, where the patient is being transferred (stroke unit and stroke center) in the form of a "stroke code call." This should accelerate onset-to-treatment time, internal "door-to-needle time," "door-to-groin-puncture time," and result in a higher thrombolysis rate ( Table 3).
The following measures should be taken by the paramedics/air rescue team in cases of suspected stroke on-site in the shortest possible time, especially if symptom onset is less than 24 h: -Secure the respiratory tract and circulation.
-Do not give antithrombotics.
-Blood pressure reduction only if systolic pressure over 220 mmHg or organ manifestations according to internal algorithms. -Advance information to stroke unit/stroke center (Stroke Code Call). -Travel with special signal for ground transport.

Stroke care in geographically remote regions
Small remote hospitals with specific expertise in acute stroke care On the one hand, the basic requirement is to move patients as quickly as possible to the nearest capable hospital for  acute stroke treatment (i.e. a stroke unit and stroke center). On the other hand, small hospitals in remote regions cannot reach the minimum mandatory number of cases for certification as a stroke unit (minimum of 200 stroke patients and 20 systemic thrombolyses per year). Due to the large distance of remote hospitals from nearest stroke unit/stroke centers (>60 min) and ensuing time delay to specific start of therapy, there is a need for small hospitals to be able to at least start acute stroke treatment including systemic thrombolysis. In principle, acute processes, medical stroke expertise, and infrastructure (CT and laboratory) should be available in these hospitals as in certified stroke units, so they can perform systemic thrombolysis and triage (LVO yes/no).
Virtual stroke expertise (telemedicine) is well suited for these hospitals, as a neurological presence on-site (24/7) cannot usually be guaranteed for hospitals of this size (Table 4).
After starting acute care in such a hospital, the patient should then be transferred to a stroke unit or stroke center to benefit from specialized treatment (number needed to treat [NNT] of stroke unit 6-8 regarding outcome in independence) in these more capable facilities. 1

Conclusions
Due to the increasing diversification of treatment methods for stroke patients, the organization of the prehospital phase needs to be adapted accordingly. These guidelines describe a prehospital organization that creates efficacious access for all stroke patients to specialized systems (stroke unit/ stroke center) allowing for appropriate and rapid treatment. The working group does not provide a conclusive recommendation on the use of the RACE score (LVO yes/no): Ultimately, the decision of which model to use will depend on local (e.g. geographical) characteristics. However, it is important that the critical time intervals of the chosen model are taken into account, measured, and evaluated.

Authors' note
Swiss Stroke Society: The guidelines were co-authored and approved by the Swiss Society for Emergency and Rescue Medicine, the Swiss Neurological Society, the Swiss Association of Paramedics, and the Inter Association of Rescue Services.