Comparison between fibrinolyzed stroke that arrived with the emergency service or other means

Abstract

Aim

Analyze the relationship between attendance times and health outcomes of people with ischemic stroke treated with intravenous fibrinolysis, comparing those attended from the emergency units of 061 ARAGON with those arriving by other means.

Method

Cross-sectional, retrospective, descriptive and association study based on a consecutive series of patients treated at the Miguel Servet University Hospital in the period 2014−16, analysing the time of care up to fibrinolysis and results of intravenous fibrinolysis, in terms of mortality and functional status at discharge. We also analysed the influence on attendance times of the protocol change that was carried out in 2016 and that included the direct warning to neurologists, instead of the receiving emergency, as before.

Results

A total of 231 patients with stroke were collected and treated with intravenous fibrinolysis. The mean age of the patients was 75.91 (±12.48). Women accounted for 52.8% of those fibrinolysed, the average age of men being lower [74.07 (±13.71) years, compared with 77.55 (±11.07) years for women]. The mean score on the NIHS scale at admission between the two groups presented significant differences (p = 0.006), being greater the affectation among those who arrived with 061 [NIHSS 13.20 ± 6.78 vs 10.7 ± 6.22]. In the comparison of times between patients who arrive or not with 061, the average time to hospital was 91.42 (±59.64) vs 93.20 (±83.73) (p = 0.731), without significant differences. However, there were significant differences in the time door needle (p = 0.046), noting that patients who are brought by 061 Aragon have better in-hospital time until fibrinolysis (better door-needle time) (67.19 (±26.03) vs 77.83 (±38.35).

In the analysis of the door needle time by years, significant differences were observed (p < 0.001), being shorter each year, with a clear shortening in 2016 compared to previous ones, reflecting the impact of the update of protocols in this time period.

Conclusions

The patients brought in by 061 were different (more affected), fibrinolysed in a greater percentage and faster. Direct notice to neurologists significantly shortened attendance times. In terms of mortality and functional status at discharge, there were no differences between the two groups.

Resumen

Objetivo

Analizar la relación entre tiempos de asistencia y resultados de salud de las personas con ictus isquémico tratadas con fibrinólisis intravenosa, comparando las atendidas desde las unidades de Emergencias del 061 ARAGÓN con los que llegan por otros medios.

Método

Estudio transversal, retrospectivo, descriptivo y de asociación a partir de una serie consecutiva de pacientes, atendidos en el Hospital Universitario Miguel Servet, en el periodo 2014−16, analizando los tiempos de atención hasta la fibrinolisis y resultados de la fibrinólisis intravenosa, en términos de mortalidad y situación funcional al alta. También se analizó la influencia en los tiempos de asistencia del cambio de protocolo que se realizó en 2016 y que incluía el preaviso directo a los neurólogos, en lugar de a la Urgencia receptora, como hasta entonces.

Resultados

Se recogieron un total de 231 pacientes con ictus a los cuales se les aplicó el tratamiento con fibrinolisis intravenosa. La edad media de los pacientes fue de 75,91 (±12,48). El 52,8% de los fibrinolizados fueron mujeres, siendo menor la edad media de los hombres [74,07 (±13,71) años, frente 77,55 (±11,07) años de las mujeres]. La puntuación media en la escala NIHS al ingreso entre ambos grupos presentó diferencias significativas (p = 0,006), siendo mayor la afectación entre los que llegaron con el 061 [NIHSS 13,20 ± 6,78 vs 10,7 ± 6,22]. En la comparación de tiempos entre los pacientes que llegan o no con el 061, el tiempo medio hasta el hospital fue de 91,42 (±59,64) vs 93,20 (±83,73) (p = 0,731), sin diferencias significativas. Sin embargo, hubo diferencias significativas en el tiempo puerta aguja (p = 0,046), observando que los pacientes que son traídos por el 061 Aragón tienen mejor tiempo intrahospitalario hasta la fibrinolisis (mejor tiempo puerta-aguja) (67,19 (±26,03) vs 77,83 (±38,35). En el análisis del tiempo puerta aguja por años, se observaron diferencias significativas (p < 0,001), siendo más corto cada año, con un acortamiento claro en 2016 respecto a los previos, reflejando el impacto de la actualización de protocolos en este periodo de tiempo.

Conclusión

Los pacientes traídos por el 061, fueron diferentes (más afectados), se fibrinolisaron en un mayor porcentaje y más rápidamente. El preaviso directo a los neurólogos acortó significativamente los tiempos de asistencia. En términos de mortalidad y situación funcional al alta no había diferencias entre ambos grupos.

Introduction

061 ARAGÓN, as an emergency medical service (EMS) and medical transport, through its emergency coordination centre, centralises information and coordination of both public and private health care resources.

Ischaemic stroke is a condition with a very heterogeneous aetiopathogenesis. A number of causes have been identified, which in combination or alone lead to cerebral ischaemia. In order to select the most suitable preventive treatment, it is important to correctly categorise the stroke event and thereby reduce the risk of recurrences¹.

Worldwide, some 15 million people suffer a stroke each year, with a mortality rate of around 30% in the first year and severely disabling sequelae in 2/3 of the survivors. Approximately 80% of these strokes are ischaemic².

The Stroke Code (SC) allows for the rapid identification, notification by means of early warning, and priority transfer of patients with acute stroke to the nearest stroke referral centre, which can offer early neurological care and reperfusion treatment if necessary³. The SC, as an example of a time-dependent emergency care device, is intended to guarantee access to reperfusion therapy, such as intravenous fibrinolysis (IF) and endovascular treatment, within a short period of time; this has been designated as the 'therapeutic window'. IF therapy is indicated within a window period of up to 4 h and 30 min from clinical onset and its benefit declines exponentially over time, with complications increasing inversely as the ischaemia progresses⁴.

The objectives the SC pursues, therefore, involve shortening the time between the onset of symptoms and access to specialised diagnosis and treatment, thereby increasing the number of stroke patients who benefit from reperfusion treatment⁵. From the perspective of SEM-061, the goal of the SC is to care for patients with a diagnosis of suspected stroke, regulating initial care and transfer, notifying the centre where the patient will be transferred ahead of time, so as to optimise time to care and the start of fibrinolysis in the cases in which it is indicated⁶.

In 2005, the SC was set up in Aragon by the SEM-061, in collaboration with the hospital neurology services of Zaragoza, and shortly thereafter it was expanded to cover the whole of Aragon.

The out-of-hospital SC is an integral part of the Stroke Care Programme in Aragon, and is coordinated with the neurology on-call service and with the emergency services of the hospitals to which the patient will be taken. Until October 2015, 061 notified the Emergency Department physicians at the hospital to which the patient was referred. Between October and December 2015, the protocol was modified and a change was implemented that became effective in January 2016 and that introduced direct, pre-notification to the neurologist.

Together with thrombectomy by catheterisation, IF with r-tPA is the only approved reperfusion treatment for acute ischaemic stroke. Response to treatment is varied and hard to predict, as it is associated with multiple factors, including the time elapsed between the onset of symptoms and its administration⁶.

Hence, stroke is a treatable, time-dependent phenomenon and ischaemic damage is potentially reversible in many cases if early reperfusion is achieved. Therefore, minimising time to care in the hyperacute phase is essential if morbidity and mortality are to be limited, which requires that we coordinate the different levels of care to ensure the fastest possible response time and have indicators to monitor it^7–12.

Aragón is an autonomous community in Spain with a population of 1,319,291 inhabitants in which the SC is well established with EMS 061; however, the type of patients using this care route and whether its results are different from those of the rest have yet to be evaluated.

The purpose of the study is to analyse the relationship between time to care and health outcomes of people with ischaemic stroke treated with intravenous fibrinolysis in the Miguel Servet University Hospital (tertiary hospital that is the reference centre for comprehensive care of ischaemic stroke in our autonomous community) comparing people treated by the Emergency Units of 061 ARAGON with those who arrive by other means, during the 2014–2016 period and the influence the change of protocol implemented in 2016 has had on these time to care.

Method

Research design

A cross-sectional, retrospective, descriptive, and association study was conducted to examine the relationship between the time of care and the results of intravenous fibrinolysis in the case series of the Miguel Servet University Hospital (HUMS) from January 2014 to December 2016.

The target population of this study was the entire population residing in Aragón who had suffered a stroke, regardless of age and sex, and who underwent fibrinolysis at the HUMS, comparing those who were initially treated by the 061 ARAGÓN Emergency Service and the rest, during the period 2014–2016. Those who were not attended by SEM-061 include those who arrived by their own means, in private or public transport, or with medical transport other than SEM-061, in particular from the fire brigade, Red Cross, or private insurers.

Data registry

Data collection was retrospective and was extracted from the medical records generated by the 061 ARAGÓN care service and the Neurology Department of the HUMS. Access to the clinical records was granted after obtaining permission from the management of 061 ARAGÓN, the hospital management, and the neurology service.

Study variables

A series of variables related to the demographic characteristics of the sample, their disease, and the care received were collected and analysed: age, sex, patients taken to hospital by 061 (yes/ no), aetiological diagnosis according to the TOAST classification, National Institute of Health Stroke Scale (NIHSS) on arrival, year, month, time of day, and day of the week.

Outcome variables were response and fibrinolysis times, as well as mortality and dependency at discharge (mRS), analysed by score (0, asymptomatic-6, death, and by 0–2 [autonomous] and 3–5 [dependent]).

Time to hospital (variable measuring the mean time from the onset of symptoms suggestive of stroke to arrival at the emergency department door); b) needle door time (variable reflecting the time, measured in minutes, from the patient's arrival at the hospital to the time at which the patient is given fibrinolysis treatment), and c) total time (mean time from the onset of symptoms to the initial bolus of IV r-tPA).

The TOAST classification was created in the early 1990s for research purposes. It classifies ischaemic stroke on the basis of aetiology into atherothrombotic, lacunar, cardioembolic, rare or infrequent cause, or undetermined cause¹³.

The NIHS scale is used almost ubiquitously by medical staff for the assessment of patients with acute stroke. It rates the degree of impairment in several dimensions (level of consciousness, eye movements, visual fields, facial paresis, upper and lower extremity paresis, sensory impairment, cerebellar impairment, dysarthria, language impairment, impairment of body and spatial perception (hemi-inattention, neglect, sensory, and visual extinction). It has a score between 0 and 42 points, with a higher score reflecting greater impairment. It has become universal and is commonly used in the hyperacute phase of stroke (initial assessment), the evaluation of treatment options (reperfusion therapies are not indicated if there is no measurable and significant neurological deficit, which is generally regarded as NIHSS > 4), and the monitoring of the patient's evolution, both by neurologists and nurses¹⁴. It has been validated in Spanish¹⁵ and correlates well with clinical severity, infarct size on neuroimaging, and prognosis.

The modified Rankin scale (mRS) is a widely used functionality scale to quantify disability after stroke. It is scored between 0 and 6 points, where 0 corresponds to no sequelae, 3 points to dependency and 6 to death)¹⁶.

In the analysis to control for the possible effects of the time of care, the following 4-h time ranges were considered for the variables "actual time of stroke onset" and "time of hospital admission": between 08:00 and 11:59 h; 12:00 and 15:59 h; 16:00 and 19:59 h; 20:00 and 23:59 h; 00:00 and 03:59 h, and from 04:00 and 07:59 h.

In our study, we applied the usual exclusion criteria for the administration of intravenous r-tPA;5 they basically consisted of: less than 4 h 30 min from the onset of symptoms, absence of extensive brain injury with irreversible ischaemic necrosis, no active haemorrhage, or high bleeding risk (including being anticoagulated), regardless of age limit.

In a few cases, intravenous fibrinolysis is performed after 4 h 30 min or when the time of onset is undetermined in patients in whom the CT brain perfusion study demonstrates a sufficient area of ischaemic penumbra (ischaemic, non-functional, but salvageable tissue). A particular case of indeterminate onset time is the wake-up stroke. In these cases, the time of onset recorded is that of the last time the patient was seen well and, therefore, in some cases we record times in excess of 270 min (4 h 30 min).

Data analysis

The statistical analysis was carried out using IBM SPSS Statistics, for Windows environment, version 22.0, and a descriptive analysis of demographic, temporal, location, and clinical variables was performed, with a description of frequencies, measures of centrality and dispersion, with analysis of normality distribution (Kolmogorov-Smirnov) when applicable. Results are given as mean ± standard deviation, otherwise specified.

In the bivariate analysis with hypothesis testing, we used comparison of proportions when both variables are qualitative (Chi-square, Fisher's exact test); comparisons of means when one of them is quantitative (Student's t-test, ANOVA, and if they do not follow normal distribution, with non-parametric tests, such as the Mann-Whitney U test or the Kruskall-Wallis test) and the correlation between quantitative variables using Spearman's correlation coefficient for non-parametric distributions. In all cases of hypothesis testing, a confidence level of 95% was considered.

Ethical considerations

This study has the approval of the Research Ethics Committee of the Autonomous Community of Aragon (CEICA) (Act n.◦ 21/2018) (C.P.-C.I PI15/276), under the rules governing access, protection, and confidentiality of patient data to public administration staff.

Results

Retrospectively, during the time period from January 2014 to December 2016 (3 years), a total of 231 stroke patients who underwent IF treatment at HUMS were collected.

Description of groups

Of these, half (113 cases; 48.2%) had been attended by SEM-061 as SC. Fig. 1 depicts the annual percentage of fibrinolyzed patients who were brought in by 061 ARAGÓN compared to those who were brought to the hospital by other means.

Figure 1.

Evolution of fibrinolyzed SC at the HUMS.

Arrival via 061 SC or by other means.

The mean age of the patients was 75.91 ± 12.48 years. Of the fibrinolyzed subjects, 52.8% were female and 47.2% were male. The mean age of the men was 74.07 ± 13.71 years and the mean age of the women was 77.55 ± 11.07 years; thus, males were significantly younger (p = 0.034) (Table 1).

Table 1.

Socio-demographic characteristics of ischaemic stroke patients treated with IF (n = 231).

	Patients
Age, mean ± SD, years	75.91 ± 12.48
Men	74.07 ± 13.71
Women	77.55 ± 11.07
	p = 0.034
Male, n (%)	109 (47.2%)
Female, n (%)	122 (52.8%)
Patients who arrive at the hospital by 061, n (%)
Yes	113 (48.2%)
No	(51.8%)

As for the aetiology of ischaemic strokes treated with rt-PA, most were of undetermined cause (36.4%) and the second most frequent cause was cardioembolic (37.2%).

Neurological and functional status

Of the sample of 231 patients, the NIHS scale was recorded on admission in 219 cases; thus, this meausre was missing in 12 cases (Fig. 2). This figure presents the distribution of the NIHS score in both groups, those admitted by 061 ARAGÓN and those admitted by other means. The mean NIHSS scores in our series were 12.21 (±6.91) for men and 11.82 (±6.36) for women; the p = 0.660 with no significant differences.

Figure 2.

Distribution of the NIHSS score upon admission across both groups, those that arrive at the hospital by 061 ARAGÓN or by other means.

Significant differences (p = 0.006) were detected in the mean NIHS scale score on admission between those transferred by 061 ARAGÓN and those who were taken by other means, with greater involvement among those who were transported by 061 (13.20 ± 6.78 vs. 10.78 ± 6.22).

There were no significant differences when comparing between those who are autonomous at discharge (eRM 0, 1, or 2) and those who are not (eRM > 2), although the difference approached significance.

It is worth noting that among those who were asymptomatic at the time of discharge (mRS 0), most had arrived by other means, and among those who were bedridden and dependent for everything when discharged (mRS 5), most had arrived by 061.

We explored whether there was any intergroup differences when it came to the mRS scale at discharge (0−1 versus 4−5; extreme values), and found that 42% of the patients with an mRS (0−1) had arrived by other means and 50% of those who exhibited an mRS (4−5) had arrived been transported by SEM 061. Consequently, the differences between groups were significant (p = 0.040) (Table 2).

Table 2.

Comparison between patients with mRS 0–1 and mRS 4–5 at discharge, depending on whether they arrived at the hospital via 061 or other means.

	CI		P
	Yes	No
mRS
0−1	31 (42.5%)	42 (57.5%)	0.040
4−5	50 (58.8%)	35 (41.2%)

Time to care

Table 3 provides a summary of the times to care. On analysing the out-of-hospital times by year, we can see that the time to hospital arrival gradually increased and there were significant differences between 2014 and 2016 (p = 0.023) (Table 4), with the means being 70.97 min [±39.17] in 2014, 91.51 min [±56.21] in 2015, and 108.37 min [±96.38] in 2016, respectively [Table 4]).

Table 3.

Summary of descriptive statistics of SC times ending with IF.

	Mean (min)	Standard deviation (min)
Time to hospital	92.77	72.85
Door-to-needle time	72.65	33.30
Total time	164.98	79.61

Table 4.

Care times by year (n = 231).

	2014	2015	2016	p
Time to hospital	Me: 70.97SD: 39.16	Me: 91.51SD: 56.20	Me: 108.37SD: 94.66	0.023
Door-to-needle time	Me: 81.30SD: 38.42	Me: 78.16SD: 32.53	Me: 61.94SD: 26.86	<0.001
Total time	Me: 152.27SD: 48.60	Me: 169.68SD: 60.48	Me: 170.08SD: 106.50	0.295

Significant differences (p < 0.001) were obtained with respect to the door-to-needle time (in-hospital SC) and decreasing year by year, with a clear reduction in 2016 in comparison to the previous years. In 2016, with a mean of 61.9 min (±47.4) and a median of 58 min, the times were clearly better, with respect to 2014 and 2015. Patients seen by SEM-061 were fibrinolyzed more often and with better door-to-needle times (67.19 ± 26.03 versus 77.83 ± 38.35) (p = 0.046) (Table 5).

Table 5.

Time comparison of patients arriving at the hospital by 061 ARAGÓN or other means.

	Time to hospital Me ± SD	Door-to-needle time Me ± SD	Total time Me ± SD
CI 061 ARAGÓN
Yes	91.42 ± 59.64	67.19 ± 26.03	158.61 ± 60.68
No	93.20 ± 83.73	77.83 ± 38.35	171.04 ± 93.98
P	0.731	0.046	0.361

Variation as a function of time factors (month, day of the week, and time segment)

We found that there were no significant differences in the times for the different months of the year or days of the week (p > 0.05).

In the time range from 04:00−07:59 h and 00:00−03:59 h, the time to hospital arrival was longer than for the other time ranges. Thus, the time to hospital arrival varied depending on the time frame (p = 0.021), at the expense of longer delays during the night-time hours. However, door-to-needle time did not differ based on the time of arrival.

With no significant differences, the distribution of patients assisted by 061 ARAGÓN was similar across the days of the week, with a maximum of 56.7% on Thursdays and a minimum of 35.5% on Fridays.

On the other hand, the high percentage of cases not transported by 061 ARAGÓN (64.5%) on Fridays is striking, albeit without achieving levels of significance (p = 0.623). August was the month with the highest percentage of cases handled by 061 ARAGON, followed by November, with 75% and 71.4% of the cases, respectively.

Finally, the months of April and February had the highest percentages of cases (76% and 68.8%, respectively) that came in by their own means, with no significant differences being detected for the cases as a whole, as we have already mentioned (p = 0.060).

Discussion

We have examined a consecutive series of patients with ischaemic stroke, treated over a period of 3 years (2014–2016), for whom treatment with fibrinolysis was indicated at the Miguel Servet University Hospital in Zaragoza. We compared those who arrived via 061 and those who did not, analysing the times-to-care and, more specifically, the relationship between these times and health outcomes, quantified as functional status at discharge (mRS scale) and mortality on admission (hospital case fatality).

Our sample contained a slight predominance of men and the mean age of the male patients was lower than the mean age of the female patients. Women were fibrinolyzed more frequently than men. In the analysis by age range, women predominated in the older age groups. In the study by Gea et al.³, the authors found a lower mean age of 71.54 ± 13.4 years, also with a higher proportion of men (55.2%). Similarly, in a recent study by Benabdelhak et al.¹⁷, the mean age was 71.1 ± 12.4 and there was a male predominance of 61.3%.

Age is the most relevant, non-modifiable, risk factor in vascular disease in general and stroke in particular. We know that, in Spain, men experience stroke at an earlier age and women have a longer life expectancy¹⁸; it is therefore reasonable to expect this distribution when studying the cases under care.

In terms of clinical severity, the patients transferred by 061 were more seriously ill, but were fibrinolyzed more frequently and with a shorter door-to-needle time. This datum answers the questions we believe to be most relevant: what patient profile activates 061 and is it better to go to the hospital with the SEM-061? To answer the first question, we can say that the SEM-061 is used by patients who are at least moderately afflicted and are not in a position to go by their own means. To the second question, we can also state that it is better to use the SEM-061 service, given that treatment is more specific and takes less time to be administered.

Furthermore, those who came by their own means had a lower NIHSS, which may explain that they were more independent in terms of functional status at discharge. We can surmise that subjects displaying less impairment are more likely to come to the ED on their own and also that home care and EMS services are less likely to identify those who are less impaired or have fewer characteristic symptoms as having a stroke and consequently, activating a SC less often. Thus, when comparing it with the study by Gea et al.³, we find that they report that in patients who, despite notifying the EMS, did not activate the SC until their arrival at the ED scored lower on the NIHS scale and had a higher frequency of stroke with mild symptoms compared to patients in whom the SC was activated by the EMS.

Ideally, all cases of suspected stroke would be channelled by activating the EMS, even those with mild symptomatology. We know that the initial deficit can increase in the following minutes or hours as collateral blood supply ceases, and that 5–10% of transient episodes, which are categorised as TIAs, will develop a cerebral infarction in the following hours or days. It is difficult to interpret why patients with less involvement or with a very high NIHSS are less likely to use SEM-061.

In our study, most patients went to hospital by other means in 2014 and 2015, while in 2016, the number of cases attended by 061 ARAGÓN rose.

With SC, pre-hospital time is added to the time-to-care times and is just as relevant, but has nevertheless received much less attention. Much more effort has been devoted to improving in-hospital times than pre-hospital times. We believe that this local analysis of the use of the EMS 061 resource is important and that the profile of patients who use these services should be investigated, as well as those who do not, and that the benefits of early, qualified care through SC should be divulged among the general population. One extremely valuable finding of our study was that while hospital care time improves year on year, pre-hospital care times do not, and the end result, as a sum of both trends, is a disappointing worsening of the situation.

We observed an association between mRS at discharge and the NIHSS scale at admission, which seems reasonable, as more severe strokes at admission have a worse overall outcome. NIHSS values in our series were 12.21 (±6.91) for men and 11.82 (±6.36) for women.

In the series by González Cano et al.¹⁹, the mean score on the NIHS scale at admission was 8.16 ± 7.28 points and was higher among females (9.6 ± 7.36 points) than among males (7.3 ± 7.1 points); the females were older.

In our study, we raised the question of whether patients who used 061 differed in their degree of impairment from those who did not.

Several studies have shown that extreme NIHSS scores (very low or very high) entail a lengthening of the door-to-needle time. In the study by Mikulik et al.²⁰, the authors noted that NIHSS scores between 7 and 24 were statistically significantly associated with a door-to-needle time ≤60 min and felt that this might explain why the borderline NIHSS score was a variability factor in medical decision making.

They used the more severely compromised 061 patients (higher NIHSS score; higher mRS), which should be taken into account when interpreting the percentages of cases that were ultimately fibrinolyzed and their discharge outcomes, in terms of demise or dependency.

In our study, we observed that there were significant differences between the door-to-needle time based on patient status on arrival, with better times among those who arrived by 061. The study by Benabdelhak et al.¹⁷, reported that 81.3% of subjects chose to call EMS and that a larger proportion of this group arrived within the first 4.5 h. As in our series, in the study by Gea et al.³, the group of subjects in whom, despite notifying EMS, the SC was not activated until arrival at the ED exhibited a systematic increase in all relevant times with respect to those patients who did activate the SC via EMS: the onset-to-treatment time was 43 min longer and the door-to-needle time was 8 min longer.

The proportion of patients receiving IF treatment (door-to-needle time) within the first 60 min following arrival at the emergency department door is the main indicator of quality of care for acute ischaemic stroke used in the literature^19,21–23. In our series, the in-hospital time to IF was better (better door-to-needle time) if they were transferred by 061 ARAGÓN; however, this was did not correlate with better outcomes in terms of dependency (mRS at discharge), perhaps because, as already reported, these were patients with more severe initial impairment.

The leading clinical practice guidelines²⁴ recommend that the door-to-needle time should be less than 60 min, and point out that the proportion of patients treated within the first hour of arrival at the ED is one of the primary indicators of quality in stroke care.

In the study by Ximénez-Carrillo Rico²⁵, the door-to-needle time after the implementation of the Plan de atención al paciente con ictus de la Comunidad de Madrid in 2009 (Stroke Patient Care Plan by the Madrid Autonomous Community in 2009) was better than ours, as its median remained below 60 min, although a trend can be seen toward a nine-minute increase between 2009 and 2015.

Some of the best in-hospital times in a single hospital published to date are those by Meretoja in Helsinki, later replicated in Melbourne²⁶. In comparison with the 85 patients previously treated, the median door-to-needle time dropped from 61 min to 46 min, achieving a median of 25 min in working hours. This study demonstrated that rapid transfer of an optimised rt-PA protocol to a different healthcare environment is feasible.

In the context of a hospital network of an entire country and not a single hospital, the result of the Dutch Audit²⁷ is especially remarkable. It included patients with acute ischaemic stroke and patients with intracranial haemorrhage during the 2014–2016 period, with a registry of more than 86,000 patients. IF treatment was administered to 10,637 patients and 1740 patients underwent intra-arterial thrombectomy. Median door-to-needle time for IF and median door-to-groin time for thrombectomy dropped from 27−25 min and from 66−64 min, respectively.

In our series, when analysing the times by year, the significant differences in the door-to-needle times are especially noteworthy, and were shorter each year, with 2016 standing out with a clear decrease compared to previous years.

In 2009, when PAIA7 was implemented, the time indicators were redefined and recording was improved. Subsequently, particularly after redesigning the organisation of emergency care in September 2015, in-hospital times have been improving as a result of the many training and reorganisation actions conducted. Clearly, there is room for further improvement, but we insist that efforts to improve pre-hospital times must go hand in hand with improvements in in-hospital times.

One measure that appears to be particularly significant is hospital pre-notification, as it shortens door-to-treatment times upon patient arrival. Activation means that patients transferred by 061 are assessed as candidates sooner and by trained doctors and the use of the radiology room is granted, reducing waiting times, and it means that the IF is seen from the outset as a therapeutic option to be decided on, reviewing possible exclusion factors such as the use of anticoagulants or a history of bleeding, etc. beforehand.

The role of advance notice in improving care times has been explored in a number of studies. The other measures that make it possible to shorten times once in hospital (clear division of labour, early access to CT, rapid decision making and infusion of rt-PA directly on the CT table, avoiding transfers and bed changes) are linked to early recognition of the SC as such and to the activation of neurologists and radiologists, so we can say that advance notice is an essential prior step.

We would like to clarify that the high percentage of cases not taken by 061 ARAGÓN attended on Fridays (which presented non-significant differences, although it is striking) cannot be accounted for by any under-reporting by the 061 ARAGÓN EMS, since the healthcare professionals of the service itself work the same way 24 h, every day.

In the study by Romero Sevilla et al.²⁸, they found no significant differences between the different subtypes of stroke and office hours, except for the day of the week variable, where the percentage of patients with lacunar stroke admitted on workdays was higher (10.3% vs. 5.3%; p = 0.025). By day of the week, 68.8% were admitted on weekdays and 31.2% on weekends.

Although in our series there were no differences in mortality and functional status between the two groups, the patients who used 061, despite showing greater severity on arrival, did not fare worse and were fibrinolyzed in a higher percentage and within a shorter time.

The limitations of this study include the lack of data on patients' functional status at 3 months and the NIHSS score at discharge, which we did not include in the analysis, as it was missing in many patients. However, it seems to us that this work provides relevant information and data regarding the SC care chain as a whole and, in that sense, we emphasise that, as we have stated, the total time is the sum of the partial times. Therefore, we must give the same importance to improving out-of-hospital times as we give to in-hospital times.

Study limitations

The limitations of this study include the lack of data on functional status at 3 months and the NIHSS score at discharge, which we did not include in the analysis because it was missing in a large proportion of patients.

Other limitations were that variables that would have been very interesting for the analysis were not collected, such as risk factors, comorbidities, and previous functional status, which would have enabled us to characterise the population better. It would also have been of interest to collect the time elapsed from the onset of symptoms to arrival at the hospital. These variables should be collected in any study of this kind, and in fact, they have been collected in our centre since 2018.

In conclusion, during the study period, the number of fibrinolyzed patients arriving at HUMS by SEM-061 increased. These patients brought by 061 differed (more affected) from those who came by other means, although there were no differences in terms of morbidity and mortality at discharge. It should be noted that the cases that were transferred to the hospital by 061 were treated more quickly, especially after modifying the protocol at the end of 2015, which included direct pre-notification to the neurologists, which appears to be an effective measure to shorten the door-to-needle time.

The role of nursing in stroke code care is fundamental in both out-of-hospital and in-hospital settings. On the one hand, during transfer, the nurse monitors the patient's vital signs and care, as well as controlling mainly the variability of blood pressure and times; secondly, once the patient arrives at the Emergency Department, they must be stabilised, the CT scan must be monitored, and once the most appropriate reperfusion treatment has been decided for the patient, post-treatment reperfusion care must be provided. This is always done with a neurologist or relevant physician, which is why it is so important to have a thorough understanding of the patient's condition.

This is why it is so important for all nursing staff to be aware of this protocol and to comply with it.

Conflict of interests

The authors have no conflict of interests to declare.