A novel emergency medical services protocol to improve treatment time for large vessel occlusion strokes.

In many systems, patients with large vessel occlusion (LVO) strokes experience delays in transport to thrombectomy-capable centers. This pilot study examined use of a novel emergency medical services (EMS) protocol to expedite transfer of patients with LVOs to a comprehensive stroke center (CSC). From October 1, 2020 to February 22, 2021, Indianapolis EMS piloted a protocol, in which paramedics, after transporting a patient with a possible stroke remained at the patient's bedside until released by the emergency department or neurology physician. In patients with possible LVO, EMS providers remained at the bedside until the clinical assessment and CT angiography (CTA) were complete. If indicated, the paramedics at bedside transferred the patient, via the same ambulance, to a nearby thrombectomy-capable CSC with which an automatic transfer agreement had been arranged. This five-month mixed methods study included case-control assessment of use of the protocol, number of transfers, safety during transport, and time saved in transfer compared to emergent transfers via conventional interfacility transfer agencies. In qualitative analysis EMS providers, and ED physicians and neurologists at both sending and receiving institutions, completed e-mail surveys on the process, and offered suggestions for process improvement. Responses were coded with an inductive content analysis approach. The protocol was used 42 times during the study period; four patients were found to have LVOs and were transferred to the CSC. There were no adverse events. Median time from decision-to-transfer to arrival at the CSC was 27.5 minutes (IQR 24.5-29.0), compared to 314.5 minutes (IQR 204.0-459.3) for acute non-stroke transfers during the same period. Major themes of provider impressions included: incomplete awareness of the protocol, smooth process, challenges when a stroke alert was activated after EMS left the hospital, greater involvement of EMS in patient care, and comments on communication and efficiency. This pilot study demonstrated the feasibility, safety, and efficiency of a novel approach to expedite endovascular therapy for patients with LVOs.

Introduction

In the United States, approximately 795,000 people sustain a stroke each year, which equates to one stroke every 40 seconds, and a death from stroke every four minutes.[1] In 2015, strokes accounted for $66 billion in costs, projected to increase to $143 billion by 2035 [2]. 87% of strokes are acute ischemic strokes (AIS) [1], and 24–38% of AIS are large vessel occlusions (LVOs) [3,4], which have greater morbidity and mortality than non-LVO ischemic strokes, but are amenable to endovascular intervention [4-7].

Since 2015, the advent of endovascular thrombectomy (EVT) has significantly improved outcomes in patients with LVOs [5]. The five initial randomized control trials investigating EVT demonstrated a number needed to treat of 2.6 to reduce a patient’s 90-day modified Rankin score (mRS) by 1 point, compared to conventional thrombolysis [5]. Minimizing time to EVT is critical to achieving these superior outcomes. 91% of LVO patients achieved functional independence at 90 days (mRS = 0–2) if EVT was performed within 150 minutes of symptom onset, but the probability of functional independence decreased by 10% over the next hour, and by 20% over each subsequent hour [8]. Every 30-minute increase in time-to-EVT reduced the probability of functional independence by 8.3% [9].

Most hospitals are not capable of performing EVT. Estimates using ambulance response times and demographic data suggest that 81% of the US population has potential access to thrombolysis within one hour, and that 56% could access EVT in the same timeframe [10]. Despite this potential, use of EVT remains low, with barriers including delayed recognition of symptoms and presentation to emergency care [10], and delays in hospital transfer that prevent a majority of patients with LVO from receiving EVT and its associated benefits [11-13].

Emergency medical services (EMS) providers face the challenge of identifying patients with stroke in general and LVO in particular, and transporting these patients to the most appropriate facilities. Patients with non-LVO strokes benefit from rapid transport to the nearest thrombolysis-capable acute stroke ready certified hospital, most of which cannot perform EVT [14]. Most EMS systems either transport all patients with suspected stroke to the nearest PSC, requiring patients with LVO to be transferred to an EVT-capable facility, or use a prehospital stroke severity score to identify patients for preferential transport to a Comprehensive Stroke Center (CSC) that can perform EVT. Direct transport to a CSC improves time-to-thrombectomy and functional outcomes for LVO [13,15], but only 26–51% of patients identified by prehospital scores actually have LVOs [16,17], resulting in inappropriate transport of non-LVO patients to sometimes overwhelmed CSCs, and transport of patients with LVOs to PSCs unable to provide definitive treatment (i.e., EVT).

With the exception of extremely rural settings, the 9-1-1 system throughout the United States is designed to deliver an ambulance within 8 minutes. The average 9-1-1 response time in Marion County is 7 minutes. By contrast, the interfacility transfer system, which would typically transport a patient with LVO from a PSC to CSC for EVT, is less widely and immediately available than the 9-1-1 emergency response system. Interfacility transfer systems employ providers trained in critical care medicine who are prepared to respond to the deterioration of complex patients during transport, but ambulances for interfacility transfer cannot generally be procured as rapidly as those for 9-1-1 response. Many patients requiring inter-hospital transport are sufficiently complex to warrant a delay in transfer in exchange for the benefit of more highly trained providers during transport. Patients with LVO are an exception, in which the importance of expedient transfer to an EVT-capable center often supersedes the method of transport.

Here we report on a pilot study of a novel protocol designed to expedite transfer and EVT for patients with LVO via 9-1-1 response ambulances.

Methods

For five months (October 2020 to February 2021), Indianapolis EMS piloted a novel “Standby-for-Transfer” protocol for patients with suspected stroke. Under this protocol, Indianapolis EMS facilitated the rapid transfer of patients with LVO to an EVT-capable CSC, instead of the conventional process of enlisting critical care transport through the transfer center. Under this protocol, paramedics who transported patients with suspected stroke to the Sidney and Lois Eskenazi Hospital ED stayed at the patient’s bedside until either dismissed by the ED physician (if no LVO was found on CT angiography) or directed to transport the patient to nearby Indiana University-Methodist Hospital for EVT (if LVO was found). This was a mixed-methods study. We report quantitative outcomes (uses of the protocol, transfer times compared to non-protocol transfers, adverse events in transfer), as well as qualitative analysis of provider impressions of the new protocol, using an inductive content analysis approach [18-20].

We included under the protocol all patients 18 years or older transported by Indianapolis EMS to Eskenazi Hospital for suspected stroke between October 1, 2020 and February 22, 2021. Eskenazi and Methodist Hospitals are large urban academic hospitals in downtown Indianapolis, located 2.0 miles apart. Patients with possible strokes taken to Eskenazi do not go directly to the CT scanner, but CT scans for those patients are completed and read by radiology at a higher priority. The respective EDs each provide care to more than 100,000 patients per year. Surrounding Marion County has a population of 903,393, which is 52% female, 11% Hispanic, 63% White, 27% Black, 2% Asian and 8% mixed or other races [21]. Median per capita income is $28,566 [21]. Indianapolis EMS is the largest ambulance service in the state of Indiana and the predominant 9-1-1 response and transport agency in Marion County, responding to approximately 120,000 EMS calls per year. Most responses are at the Advanced Life Support level; ambulances are staffed with one paramedic and one emergency medical technician.

Under the pilot protocol, Indianapolis EMS paramedics remained at the bedside in the ED after transporting any patient with a dispatch code of “stroke” or a primary provider impression of “stroke,” “altered mental status,” or “weakness,” until dismissed by the ED physician or bedside neurologist, or directed to transfer the patient to Methodist Hospital for EVT (Fig 1). Inclusion criteria were selected based on historical analysis to optimize sensitivity for stroke detection. In patients with possible LVO, EMS providers remained at bedside through the neurological assessment and CT angiography. If thrombolysis was indicated, an alteplase bolus was given and the infusion started. Prior to protocol implementation, EMS providers were trained on pump management and indications to discontinue thrombolysis infusion (e.g., motor vehicle collision or other trauma). If an LVO was detected via CT angiography, the patient was returned to the same EMS ambulance with the same crew for expedited transfer to Methodist Hospital, with which an auto-accept agreement was previously arranged for LVO EVT candidates. Care was provided by the EMS crews; additional nursing or physician support were not sent with the patient as part of the protocol. The ED physician called the transfer center to communicate patient information, but not to arrange transfer itself.

Fig 1

Novel protocol flowsheets.

A) Brief protocol for Indianapolis EMS providers and B) Detailed in-hospital flowsheet.

Throughout the five-month pilot, we queried EMS and hospital electronic medical records and noted patient demographics, instances of protocol use and associated transfers, adverse events during transport, and transfer times. For patients who were transferred, we recorded symptoms, last known well time, National Institutes of Health Stroke Score (NIHSS), time of thrombolytic administration, transfer time, and the patient’s final diagnosis.

To estimate protocol-related improvements in transfer times, we compared protocol LVO transfers with other emergent critical care transfers to Methodist Hospital arranged via the conventional transfer process over the same period. The control patients were transferred emergently with the same level of urgency as patients with LVOs. We surveyed EMS providers, and ED physicians and neurologists at both sending and receiving institutions via e-mail. Respondents were asked to respond to the following about the pilot protocol:

Tell me about how this process went for you.

Tell me how we can improve this process.

Tell me how this process compares to what you’re used to.

We described the demographics, past medical history, and clinical characteristics of eligible patients. We calculated the time in minutes from the ED physician’s decision to transfer an LVO patient to their arrival at Methodist Hospital (median and IQR), and corresponding times for emergent non-protocol transfers to the same facility. We compared transfer times for the two groups with a Wilcoxon rank-sum test using Prism GraphPad (San Diego, California).

Qualitative data were analyzed using Microsoft Word and an inductive content analysis approach [22,23]. Three physicians (one female ED attending and EMS medical director, one male EMS fellow, and one female ED resident) read and openly coded each response as they were completed. All three surveyors had an established relationship with the providers through their professional roles. All providers (EMS and in-hospital) were alerted to the objectives of the study via electronic-mail prior to the start of the study. The three researchers came together to discuss their individual codes and identify preliminary concepts and themes. Concepts identified in each response were tested in subsequent surveys. The iterative process of coding, recoding, and sub-coding continued until all responses were analyzed and the major themes were identified. Given the design of this mixed-methods study, we did not continue data collection until we reached theoretical saturation. Instead, our goal was to analyze all the responses obtained, which we did. However, by the end of qualitative data analysis we believe we reached theoretical saturation as no new concepts were being identified in the data [24]. Disagreement between researchers was resolved through discussion. Detailed accounts of this coding process were documented in the field journal as part of the audit trail [25].

We reviewed prehospital and in-hospital charts of all patients transferred under the pilot protocol for adverse events, including patient deterioration secondary to transfer by non-critical care trained EMS providers, motor vehicle collisions, and intracranial hemorrhage.

This study was approved by the Indiana University Institutional Review Board (protocol #2008585011).

Results

Quantitative analysis

During the study period, 42 patients were brought to Eskenazi Hospital by Indianapolis EMS and evaluated for stroke. Under the “Standby-for-Transfer” protocol, Indianapolis EMS transferred 4 patients with LVO to Methodist Hospital for EVT. Time from patient arrival to administration of tPA did not change significantly when compared to patients in the same time period in the prior year (Table 1).

Table 1

Descriptive statistics of patients receiving alteplase during a period one year prior to the protocol (Oct 1, 2019 to Feb 28, 2020) and during the protocol (Oct 1, 2020 to Feb 28, 2021).

	Pre-Protocol	During Protocol	p-value
Number of Patients	18	14
NIHSS—Median (IQR)	5 (3–12)	17 (11–26)	<0.001
Door to Needle minutes Median (IQR)	52 (50–67)	46 (41–60)	0.325
Arrival Method			0.265
POV	8 (44.4%)	9 (64.3%)
EMS	10 (55.6%)	5 (55.75%)

Patient characteristics are described in Table 2 with further detail of the patients who were transferred in Table 3. Review of patient charts revealed no adverse events to patients or providers associated with transfers under the pilot protocol.

Table 2

Characteristics of patients transferred during the protocol.

Age—mean (SD)	60.6 (12.7)
Sex
Male	22/42 (52.4%)
Female	20/42 (46.6%)
Race and Ethnicity
Asian or Pacific Islander	3/42 (7.2%)
Black or African American	23/42 (54.8%)
Hispanic or Latino	2/42 (4.8%)
White	13/42 (31.0%)
Past Medical History
Atrial Fibrillation	9/42 (22.5%)
Diabetes	21/42 (51.2%)
Hypertension	31/42 (75.6%)
Hyperlipidemia	18/42 (45.0%)
Prior Stroke	19/42 (48.7%)
Tobacco Use	29/42 (74.4%)
Initial NIHSS (median, IQR)	7.0 (3.0–13.8)
Hours since last known normal (median, IQR)	2.3 (1.0–5.3)
Acute Ischemic Stroke (including LVO)	15/42 (35.7%)
Large Vessel Occlusion	4/42 (9.5%)

Demographics, medical history and clinical presentations of patients in the study.

Table 3

Characteristics of patients transferred using the protocol.

Gender	Age	Paramedic RACE Scale	Symptoms	LKW	Time to Arrival at Eskenazi ED	NIHSS	Time from ED Arrival to tPA	Location of LVO	Door-in-door-out time*	Disposition
Male	72	6	Right-sided weakness, facial droop and aphasia	03:30	310 min	17	Not given	Left MCA at M1/M2 junction	54 min	Acute rehabilitation facility
Male	47	5	Left sided weakness	16:00	56 min	17	46 min	Right M2	76 min	Long-term care facility
Male	33	undocumented	Right hemiparesis and aphasia	13:00	105 min	17	40 min	Left M2	50 min	Discharged home
Female	55	6	Syncope, gaze deviation, right sided weakness	11:45	31 min	22	Not given	Left ICA terminus	54 min	Died in the hospital

*Transfer time was the time the patient left the Eskenazi ED; LKW, last known well (time); NIHSS, NIH stroke scale; tPA, tissue plasminogen activator; LVO, large vessel occlusion; MCA, middle cerebral artery; ICA, internal carotid artery.

The median time from the Eskenazi ED physician’s decision to transfer to patient arrival at Methodist Hospital was 27.5 minutes (IQR 24.5–29.0). During the same time period, 38 patients were emergently transferred from Eskenazi to Methodist Hospital for reasons other than LVO, with a median time from decision-to-transfer to arrival of 314.5 minutes (IQR 204.0–459.3) (data with times and diagnoses included in S1). The difference in transfer times between the two groups was statistically significant at p<0.001. Non-LVO transfers from Eskenazi to Methodist Hospital were most commonly due to a need for a particular specialty or facility (e.g., the cardiac catheterization laboratory at Eskenazi Hospital was unavailable for emergent angiography, or an operating room was unavailable for emergent surgery).

Qualitative analysis

We sent surveys to 66 consecutive providers involved in the care of study patients, including EMS providers, ED physicians, neurologists, and nurses. EMS providers were surveyed every time the protocol was activated. Physicians and nurses were surveyed when a patient was transferred via EMS. No repeat interviews were carried out. We received responses from 29 EMS providers, 11 ED physicians (3 residents and 8 attendings), 7 neurologists (3 residents and 4 attendings), 1 neurosurgeon/interventionalist, and 3 nurses. Participants did not provide feedback on the findings.

Qualitative analysis of provider responses demonstrated six themes: lack of awareness of a new protocol, communication, smooth process, impediment to using the protocol when a stroke alert was activated after EMS left the hospital, involvement of EMS in patient care, and efficiency. Each theme is discussed in detail below.

Lack of awareness

Lack of awareness of a new protocol was a common response from both paramedics and physicians, especially in the first week of protocol use (4 of 11 survey responses). Responses from earlier EMS runs include paramedics saying “I forgot about the protocol” or “I didn’t know [‘Standby-for-Transfer’] was live.” One EMS crew member mentioned that when a decision was made to transfer a patient, “no one seemed to know what to do.” One emergency medicine physician at Methodist Hospital remarked “[the] process seemed to work because I didn’t know there was a process.” Similarly, one paramedic commented that the Methodist ED seemed unaware that a stroke patient was a transferred patient, rather than coming directly from a scene. Overall, numerous responses suggested that not all team members (including paramedics, physicians, and nurses) at either Eskenazi or Methodist Hospitals were aware of the protocol. Later in the study, EMS providers were more likely to be aware of the protocol, but continued to perceive in-hospital providers as lacking awareness of the protocol.

Communication

Communication was a common theme mentioned by providers. While several paramedics noted good communication, specifically from physicians to the paramedics, others highlighted a lack of communication between the different team members. Specifically, one paramedic complained, “no one really kept us informed” as the Eskenazi ED providers were assessing a patient for possible transfer. Another paramedic reported, “I reminded everyone in the room of the process” and went on to state they felt the process went smoothly. One ED physician recommended “encourage the EMS crew to check in with the emergency department physician before dispersing,” on a case where a stroke was activated after the EMS crew had already left.

Smooth process

Ten different paramedics and additional physicians commented that the overall process was “smooth.” One paramedic, caring for a patient who did not require transfer, commented “the process was very smooth and we were only there [at Eskenazi] for 15 minutes.” An ED physician at Eskenazi who was caring for an LVO patient who was transferred using the protocol described the process as “seamless,” and said they “almost didn’t notice it happening.” Three neurologists provided similar assessments.

Impediment to using the protocol when a stroke alert was activated after EMS left the hospital

This theme was raised several times early in the pilot. In one case, an ED resident noted that they decided to activate a stroke alert only after obtaining collateral information from the patient’s family, by which point Indianapolis EMS had already left. In another case, an ED resident mentioned that “language barriers and misinformation” led to delayed activation of a stroke alert, which occurred after paramedics had already departed. This theme was also discussed by one emergency medicine attending and one paramedic, possibly for the same patient case(s). This theme was not seen in responses after the first week of the protocol.

Involvement of EMS in patient care

Numerous EMS providers made positive comments regarding their increased involvement in patient care when the protocol was used. One paramedic commented, “it was a very educational and fun experience.” Another paramedic found it rewarding to witness patient outcomes and stated that the process gave them “closure.” Several paramedics found it educational to observe patient care after ED arrival, including discussions over neuroimaging. Overall, EMS crew members made positive remarks regarding their increased involvement in patient care.

Efficiency

Many comments touched on efficiency and inefficiency. Several paramedics and in-hospital providers noted inefficiencies related to the protocol, including extended EMS wait time, delays in transporting patients to definitive care, and delays in transfer center communication. One paramedic commented:

“We were out of service for an hour missing several incidents in our area for a patient that likely wasn’t even eligible for Methodist’s advanced capabilities. If it took 50 minutes to determine if this patient needed intervention, what difference does the 5–10 minutes it would take for an ambulance to respond to Eskenazi make? Not to mention, the hospital would have a difficult time starting all of the interventions needed in that interval and contacting Methodist to confirm approval of transport in a 10-minute time span…it’s a waste of time and resources.”

This sentiment was echoed by other paramedics, as well as by an ED attending physician.

Conversely, other paramedics and physicians frequently cited protocol efficiency. One ED attending responded “it was nice that the patient got to definitive care faster.” A neurology resident at Eskenazi also commented on the ease of having paramedics available at bedside to transfer the patient, rather than arranging and waiting for a separate crew, stating “ultimately, the patient likely received a time-sensitive treatment more quickly than they would have if it weren’t for EMS being on standby.” Furthermore, an emergency medicine resident physician at Methodist Hospital stated the process was “similar if not more efficient than normal stroke alerts…because neurology knew about it even before I did.” A neurology resident at Methodist commented that the interventional radiologists were “totally prepared for the patient on arrival.”

Discussion

To our knowledge, this is the first study using the United States 9-1-1 response system to expedite transfer of LVO patients for EVT. While this is a pilot study, our data suggest that this protocol can be used to successfully improve time-to-EVT. For EMS systems, using 9-1-1 vehicles for emergent interfacility transfer is unusual, as the priority of the 9-1-1 system is to respond as rapidly as possible to out-of-hospital emergencies. In the case of LVO transfers, however, the relatively small number of patients requiring emergent transfer to EVT-capable centers (as compared to total daily EMS call volume), and the large benefits of earlier EVT for these patients, warranted investigation of such an approach.

While EMS systems vary widely, we believe this approach can be adapted to improve time-to-EVT and corresponding neurological outcomes for patients with LVO. Many studies have demonstrated delays to EVT that are exacerbated when patients initially present to a facility that is not EVT-capable [11-13]. We were interested to note in our data that the use of the protocol led to improvements in time-to-tPA, beyond the improved expediency of utilizing the 9-1-1 ambulance for transfer. Further studies are needed to clarify what types of transfer systems are used nationally, and to what extent delays in transfer are attributable to the limited availability of conventional interfacility transport. While more complex patients (e.g., on mechanical ventilation or requiring multiple infusions) may require a higher provider level of training, this pilot study demonstrates the feasibility of training paramedics to transport LVO patients with ongoing thrombolytic infusions.

EMS systems considering implementation of this protocol must consider potential impact on 9-1-1 response times if an ambulance is out of service for “Standby-for-Transfer.” That impact will likely vary widely from system to system, but examination of a similar approach in Ireland showed similar positive results without adverse impact to their ambulance system [26]. In this study, we did not transfer any patients with intracranial hemorrhage via the pilot protocol. Although a similar approach could be considered in other time-sensitive conditions such as intracranial hemorrhage, trauma and ST segment myocardial infarction, potential benefits of expedited transfer must be weighed against the burden of keeping EMS crews in the ED.

Given the nature of this pilot study, we anticipated some initial period of adjustment. Our qualitative survey results demonstrated a perceived lack of awareness and communication among both in-hospital and prehospital providers. Unsurprisingly, that lack of awareness disappeared in responses over time. We anticipate that communication between in-hospital and prehospital providers would continue to improve with an extended implementation of the protocol. We were pleased that a number of providers commented on the “smoothness” of the novel approach.

One goal of the protocol was to enhance the sense of patient ownership among paramedics, as well as providing education in stroke evaluation, and feedback on patient outcomes. Survey responses indicated that at least some prehospital providers appreciated these opportunities. While it is often impractical to take providers out of service for extended periods, our study shows that there may be specific instances in which longer periods of EMS involvement in the ED can benefit both patients and prehospital providers.

Our protocol did not account for patients who self-presented to the ED, or who were already hospitalized when the need for transfer was identified. In one instance, the protocol was not used because a stroke alert was activated on an ED patient after EMS had already left the hospital.

To improve efficiency in systems with less paramedic capacity, EDs might engage the 9-1-1 system to transfer patients with LVOs, without requiring paramedics to wait at bedside. Through collaborative engagement of EMS medical directors, prehospital providers, neurologists, and ED physicians, we hope to continue to improve our systemwide response with the goal of significantly improving outcomes for patients with LVO by safely reducing time-to-EVT.

Limitations

This study was limited by the small number of patients for whom the protocol was activated. As a pilot study, the protocol was only in effect for five months. While we were able to assess feasibility, improvements in transfer time, and impact on the EMS system, we were unable to directly assess impact on neurological outcomes. Because we conducted the pilot study during a period when the sending facility (Eskenazi Hospital) was temporarily without thrombectomy capability due to renovations, we cannot directly compare transfer times for LVO patients before and during the study period, since LVO patients prior to the study period could receive thrombectomy at Eskenazi Hospital. However, we used as our control patients who were emergently transferred from Eskenazi to Methodist during the same time period via the conventional process. Finally, while we believe this study provides compelling evidence in favor of using the 9-1-1 system to expedite the transfer of patients requiring emergent thrombectomy, we acknowledge that EMS systems vary widely across the country, and that our approach will require modification to match the resources and practices of any system in which it would be implemented.

Conclusion

A “Standby-for-Transfer” protocol, using the 9-1-1 emergency response system to expedite transfer of LVO patients to a comprehensive stroke center for endovascular thrombectomy, demonstrated feasibility and improved transport times, and has the potential to improve patient outcomes for an extremely time-sensitive critical condition.

Emergent transfers using the conventional transfer system.

(XLSX)

Click here for additional data file.

13 Aug 2021

PONE-D-21-24078

A Novel Emergency Medical Services Protocol to Improve Treatment Time for Large Vessel Occlusion Strokes

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Reviewer #1: The study of Glober et al is focus on an emergency medical services (EMS) protocol to expedite transfer of patients with LVOs to a comprehensive stroke center (CSC). In wich paramedics, after transporting a patient to non-CSC with a possible stroke remained at the patient’s bedside until released by the emergency department or neurology physician.. If indicated, the paramedics at bedside transferred the patient, via the same ambulance, to a nearby thrombectomy capable. They concluded that “Standby-for-Transfer” protocol demonstrated feasibility and improved transport times.

I agree with the authors that time is brain and improving times in all of the steps is crucial in acute stroke management. Otherwise, there is lack of information in different parts of the protocol that may clarify attention to suspected stroke patients.

I have some major and minor concerns:

The statistical analysis is poor of data and results are based on comparison on groups with different underlying acute medical conditions. I think that including more details in your results would improve the quality of your research .

-Please provide information about the internal protocol of your institution concerning how transfer of a suspected stroke is managed . Are there different steps in emergency room or is the patient moved Directly to perform a Computed Tomography? , Include the reference of Noreen Kamal et al. 2017

-Because this is a study conducted to analyze the influence of paramedicals activity in work flow, I would like to see paramedical scores of suspected strokes for identifying patients like “stroke-like symptoms (termed FAST-positive) ,The RACE Scale ( see work of Robert L Dickson et al . Prehosp Emerg Care. 2019 .) or any other score that are often used by paramedics for screening strokes in your community

-Were there any case of Intracranial hemorraghe stroke ( ICH) and did these patients benefit of your protocol?

-Please include door-in-door-out (DIDO) times of each group , and reference the work from “Ambulance waiting and associated work flow improvement strategies of Eva Gaynor”

-Did your protocol may help to improve times of intravenous fibrinolysis with or without LVO ? Can you provide data of door-to-needle time in those eligible for thrombolysis and can you compare these patients with a historical control group ?

The authors compare patients with suspected strokes with patients with other conditions, please include in the discussion how your protocol may benefit main emergencies and not only suspected LVO strokes .

Reviewer #2: This manuscript reports on outcomes of a 5 month long pilot study using a novel emergency medical services protocol to improve treatment time for large artery occlusive stroke. EMS paramedics EMS providers remained at the bedside until the clinical and imaging assessment of a suspected stroke patient were complete. If indicated, the paramedics at bedside transferred the patient, via the same ambulance, to a nearby thrombectomy capable comprehensive stroke centre (CSC) with which an automatic transfer agreement had been arranged. On quantitative analysis the study demonstrated a significant reduction in median time from decision-to-transfer to arrival at CSC compared with other acute non-stroke emergent interhospital transfers during same time period.

A major limitation of the study is the inability to directly compare the decision-to-transfer times for LVO patients during the pilot study to those prior to the study. Transfer times for other acute non-stroke emergent interhospital transfers during same time period was instead used as a comparison. Presumably these other acute non-stroke emergent interhospital transfers would be undertaken with the same level of urgency as transfer of acute stroke patients – this needs to be clarified and clearly stated, otherwise the comparison is futile.

A further limitation is lack of comparison of other time metrics such as door to needle and door to decision time in stroke patients prior to and during the pilot study.

Were patients transferred with accompanying nursing staff/physicians, or solely the EMS personnel? This requires clarification.

The qualitative analysis of the pilot study is interesting, with useful organization of findings into major themes. This section of the results would however benefit from being shortened.

**********

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Reviewer #2: No

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15 Sep 2021

Thank you so much for the thoughtful comments from reviewers. We are pleased to resubmit our article A Novel Emergency Medical Services Protocol to Improve Treatment Time for Large Vessel Occlusion Strokes with the following responses:

Please ensure that your manuscript meets PLOS ONE's style requirements.

We reviewed the style requirements and revised accordingly.

Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository

We included a supplemental file with our data.

We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 2 in your text; if accepted, production will need this reference to link the reader to the Table.

We edited to include reference to Table 2 in our text.

Please give a complete account of qualitative data analysis approach, such as the methods for research triangulation or coding systems used to select significant sections from participant statements and the process of theme derivation. Information on software used in this analysis should be provided. Statistical analysis of quantitative parameters should be included in as much as possible.

We included details of the software used and statistical analysis used on the quantitative data.

The statistical analysis is poor of data and results are based on comparison on groups with different underlying acute medical conditions. I think that including more details in your results would improve the quality of your research.

We listed the limited number of patients in our analysis as a limitation in the manuscript. While it does limit our conclusions, we hope that the presentation of a novel approach and our findings presented here garner interest in the manuscript. We have included more detail on the comparison group and their different medical problems. Specifically, we included in S1 the transfer time for each patient used in the control group and also the medical reason for emergent transfer.

Please provide information about the internal protocol of your institution concerning how transfer of a suspected stroke is managed. Are there different steps in emergency room or is the patient moved Directly to perform a Computed Tomography?

We detailed the protocol in the emergency room.

Because this is a study conducted to analyze the influence of paramedicals activity in work flow, I would like to see paramedical scores of suspected strokes for identifying patients like “stroke-like symptoms (termed FAST-positive) ,The RACE Scale ( see work of Robert L Dickson et al . Prehosp Emerg Care. 2019 .) or any other score that are often used by paramedics for screening strokes in your community

We included the RACE scale by paramedics of each patient in table 2.

Were there any case of Intracranial hemorraghe stroke ( ICH) and did these patients benefit of your protocol?

There were no cases of intracranial hemorrhage stroke transferred via this protocol. We added commentary in the discussion section.

Please include door-in-door-out (DIDO) times of each group, and reference the work from “Ambulance waiting and associated work flow improvement strategies of Eva Gaynor”

We included DIDO times for the transferred patients add added the suggested reference.

Did your protocol may help to improve times of intravenous fibrinolysis with or without LVO ? Can you provide data of door-to-needle time in those eligible for thrombolysis and can you compare these patients with a historical control group?

We included further data on time to intravenous fibrinolysis during the protocol and before the protocol.

The authors compare patients with suspected strokes with patients with other conditions, please include in the discussion how your protocol may benefit main emergencies and not only suspected LVO strokes.

We included commentary in the discussion section.

A major limitation of the study is the inability to directly compare the decision-to-transfer times for LVO patients during the pilot study to those prior to the study. Transfer times for other acute non-stroke emergent interhospital transfers during same time period was instead used as a comparison. Presumably these other acute non-stroke emergent interhospital transfers would be undertaken with the same level of urgency as transfer of acute stroke patients – this needs to be clarified and clearly stated, otherwise the comparison is futile.

We included further detail of the type of control patients and clearly stat that the control patients were transferred with the same level of urgency.

A further limitation is lack of comparison of other time metrics such as door to needle and door to decision time in stroke patients prior to and during the pilot study.

We added data on door to needle time prior to and during the pilot study. Because of the nature of the study (occurring during an Eskenazi thrombectomy suite remodel) we are not able to provide door to decision time outside of the study.

Were patients transferred with accompanying nursing staff/physicians, or solely the EMS personnel? This requires clarification.

The patients were transferred with EMS personnel. We clarified in the text.

The qualitative analysis of the pilot study is interesting, with useful organization of findings into major themes. This section of the results would however benefit from being shortened.

We shortened the qualitative analysis section.

13 Oct 2021

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Karen M Doyle, PhD

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: (No Response)

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: (No Response)

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: (No Response)

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors made some efforts to improve the quality of the manuscript, but there is still lack of data and robust statistical analysis.

As explained by the author “ Time from arrival via EMS to administration of tPA improved from median time of 59.8 minutes when the protocol was not in use to 43 minutes during the protocol (p<0.01).”

I cannot see were this affirmation comes from. This data should be demonstrated through a table of case-control analysis . Because the analysis of modified transfer times was conducted during 5 months, I would suggest to compare this data with a hystorical control group of at least 5 months in the same period of the last year .

It is of outmost importance to incorporate number of patients treated with iv fibrinolysis as well as door-to-needle time (DNT) to iv fibrinolysis between both groups.

“Table 1. Patient Characteristics” should be changed to a comparison analysis of historical control group vs analyzed group.

The most important part of the manuscript is about reduction of times of treatment based on your protocol, in page 12 “(data with times and diagnoses included in S1) I guess that this means supplementary material S1 but I cannot find any table or figure in S1 including these KEY data.

So I ask again about my two previous questions to be answered

“Please include door-in-door-out (DIDO) times of each group, and reference the work from “Ambulance waiting and associated work flow improvement strategies of Eva Gaynor”

We included DIDO times for the transferred patients add added the suggested reference.

WHERE IS THIS DATA?

Did your protocol may help to improve times of intravenous fibrinolysis with or without LVO ? Can you provide data of door-to-needle time in those eligible for thrombolysis and can you compare these patients with a historical control group?

We included further data on time to intravenous fibrinolysis during the protocol and before the protocol.

WHERE IS THIS DATA?

On the other hand the part of results that includes literally comments in pages 13 to 17 “ “ , I suggest to be included in a supplementary material because it does not improve the quality of the manuscript.

The aim of the study should be to incorpotate the protocol “Standby-for-Transfer” to improve times of treatment for iv fibrinolysis and transfer times of LVO strokes, so the results and the discussion should be related to this purpose.

Reviewer #2: All comments or recommendations from this reviewer have been addressed by the authors of the manuscript.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

14 Dec 2021

Thank you for the reviewers’ comments. We are pleased to resubmit our article A Novel Emergency Medical Services Protocol to Improve Treatment Time for Large Vessel Occlusion Strokes with the responses listed below.

The authors made some efforts to improve the quality of the manuscript, but there is still lack of data and robust statistical analysis. As explained by the author “ Time from arrival via EMS to administration of tPA improved from median time of 59.8 minutes when the protocol was not in use to 43 minutes during the protocol (p<0.01).” I cannot see were this affirmation comes from. This data should be demonstrated through a table of case-control analysis. Because the analysis of modified transfer times was conducted during 5 months, I would suggest to compare this data with a hystorical control group of at least 5 months in the same period of the last year.

It is of outmost importance to incorporate number of patients treated with iv fibrinolysis as well as door-to-needle time (DNT) to iv fibrinolysis between both groups. “Table 1. Patient Characteristics” should be changed to a comparison analysis of historical control group vs analyzed group.

We added a table 1 to show this for period from Oct-Feb 2019/2020 compared to Oct-Feb 2020/2021. When we used a historical control (as opposed to 5 months pre protocol and 5 months during protocol).

The most important part of the manuscript is about reduction of times of treatment based on your protocol, in page 12 “(data with times and diagnoses included in S1) I guess that this means supplementary material S1 but I cannot find any table or figure in S1 including these KEY data.

We included Table S1 at the end of the body of the manuscript (as opposed to a separate upload) to hopefully facilitate reviewer’s ability to see the data.

So I ask again about my two previous questions to be answered

“Please include door-in-door-out (DIDO) times of each group, and reference the work from “Ambulance waiting and associated work flow improvement strategies of Eva Gaynor” We included DIDO times for the transferred patients add added the suggested reference.

WHERE IS THIS DATA?

The reference to Eva Gaynor is in paragraph 3 of the discussion section, sentence 2.

Column 10 of Table 3 outlines the DIDO times for the stroke patients who were transferred. If the reviewer is referring to DIDO times for control patients, as discussed in the manuscript this data does not exist. The pilot study occurred in a time period when the EVT suite for the sending facility was being remodeled. In the year prior, there were no DIDO times because the patients were not being transferred. Similarly, DIDO times are not commonly collected for non-stroke emergent transfers as this is not a common metric in other pathologies.

Did your protocol may help to improve times of intravenous fibrinolysis with or without LVO ? Can you provide data of door-to-needle time in those eligible for thrombolysis and can you compare these patients with a historical control group? We included further data on time to intravenous fibrinolysis during the protocol and before the protocol.

WHERE IS THIS DATA?

As mentioned above, we added a table 1 to show this for period from Oct-Feb 2019/2020 compared to Oct-Feb 2020/2021. The time to intravenous fibrinolysis is additionally described in paragraph 1 of the results section.

On the other hand the part of results that includes literally comments in pages 13 to 17 “ “ , I suggest to be included in a supplementary material because it does not improve the quality of the manuscript.

We respectfully submit that a mixed methods approach is legitimate and highlights the important provider reactions to the pilot of a radically different protocol from that commonly used. For other groups attempting to pursue or operationalize a similar protocol in their system, understanding cultural context and reactions is important, not supplemental.

The aim of the study should be to incorporate the protocol “Standby-for-Transfer” to improve times of treatment for iv fibrinolysis and transfer times of LVO strokes, so the results and the discussion should be related to this purpose.

We did not find that the protocol improved times to fibrinolysis but we attempted to further emphasize the focus on improved time-to-EVT in the discussion section. We hope that by adding the new Table 1 in the results section we adequately addressed this concern regarding the results.

Submitted filename: Response to Reviewers Plos R2 12_13_21.docx

Click here for additional data file.

14 Feb 2022

A Novel Emergency Medical Services Protocol to Improve Treatment Time for Large Vessel Occlusion Strokes

PONE-D-21-24078R2

Dear Dr. Glober,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Karen M Doyle, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: (No Response)

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: (No Response)

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: (No Response)

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors improved the quality of the paper and replied to my concerns satisfactory so I agree to approve the submitted paper to be published .

Reviewer #2: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

16 Feb 2022

PONE-D-21-24078R2

A Novel Emergency Medical Services Protocol to Improve Treatment Time for Large Vessel Occlusion Strokes

Dear Dr. Glober:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

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