eISSN: 1509-572x
ISSN: 1641-4640
Folia Neuropathologica
Current issue Archive Manuscripts accepted About the journal Special Issues Editorial board Reviewers Abstracting and indexing Subscription Contact Instructions for authors Ethical standards and procedures
SCImago Journal & Country Rank
vol. 60
Review paper

The application of pre-hospital first aid mode in patients with acute stroke: meta-analysis

Xiaoting Zhu
Rong Niu
Fangfang Bai
Zhufeng Zhang

Emergency Department of Sandun Hospital, Zhejiang Hospital Affiliated to Zhejiang Medical University, Hangzhou, China
Folia Neuropathol 2022; 60 (3): 284-291
Online publish date: 2022/06/29
Article file
- The application.pdf  [0.15 MB]
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
PlumX metrics:


Stroke is the most common cause of death and the leading cause of sexual disability in adults worldwide [3]. The World Health Organization calls stroke the ‘epidemic of the 21st century’ [21]; in the United States, about 795,000 adults experience a new or recurrent stroke every year [2]. Stroke not only has a high incidence, but also causes high mortality, high disability rate and complications, which seriously endanger the life safety and quality of life of patients [14].

The main principle for the treatment of acute stroke is to implement thrombolytic therapy as soon as possible, and experimental and systematic evaluation studies have shown that the effect of intravenous injection of tissue plasminogen activator (tPA) on patients with acute stroke depends on the time from onset to injection of tPA [8,15,19], and the treatment time window for acute stroke is 6 hours from onset to admission. However, previous studies have found that most patients with acute stroke receive treatment beyond the most effective time window. For example, the median time from onset to treatment of acute stroke patients in the Get-With-The-Guidelines Center of the United States is 144 minutes [22]; the median time from onset to treatment of acute stroke patients in the European Research Centre is 140 minutes [26]. On the other hand, effective emergency measures have significantly improved the prognosis and complications of patients [16]. Therefore, rapid and effective pre-hospital emergency measures play an important role in improving the emergency effect and prognosis of patients with acute stroke. On the surface of a large number of original studies, the implementation of pre-hospital and in-hospital emergency measures can shorten the thrombolysis time of patients with acute stroke [23,28], improve limb motor ability, daily living ability and neurological function [4,29], and also the prognosis of patients. However, there is a lack of systematic evaluation research in this field, so it is necessary to carry out this study.

In this study, we aimed to systematically evaluate the application effect of pre-hospital and in-hospital emergency mode in patients with acute stroke through systematic retrieval of public databases, so as to provide reference for the promotion and improvement of emergency mode of acute stroke.

Material and methods

Literature retrieval strategy

Following the guidance manual of PRISMA, three English databases including PubMed, EMBASE and Cochrane Library, and three Chinese databases including CNKI, Wanfang and VIP were systematically searched. The search concerned the period from database construction to 30 October 2021. The English database retrieval strategy includes the following keywords: ‘stroke’; ‘pre-hospital’, ‘in-hospital’, and ‘emergency care’. The Chinese database retrieval strategy includes the following keywords: ‘stroke’, ‘cerebral infarction’, ‘cerebral haemorrhage’, ‘pre-hospital emergency care’, ‘hospital emergency care’, and ‘integrated emergency care’.

Inclusion and exclusion criteria

Inclusion criteria: 1) patients diagnosed as cerebral haemorrhage or stroke by clinical diagnosis and confirmed by computed tomography (CT) or magnetic resonance imaging (MRI); 2) the observation group adopted pre-hospital first aid or in-hospital first aid or pre-hospital and in-hospital integrated first aid measures, while the control group adopted conventional first aid methods for cerebrovascular diseases; 3) outcome indicators include first aid time (min), first aid effect (including efficiency, disability and mortality), complications and prognosis after first aid. The Barthel index was used to evaluate the prognosis after first aid. Reporting one of these outcome indicators is sufficient for inclusion in this study; 4) case-control study; and 5) Chinese literature only included core journal articles.

Exclusion criteria: 1) non-original studies such as systematic review and case report; 2) lack of the conventional emergency control group; 3) literature with incomplete outcome indicators and no data analysis.

Literature screening and data extraction

Two researchers separately screened the literature according to the inclusion and exclusion criteria. When the two people were inconsistent, the third researcher was consulted for discussion to reach a unified opinion. After literature screening, the data were extracted by two researchers, including literature information, demographic characteristics of the subjects, first aid methods, related outcome indicators, research types and other information.

Quality evaluation

Newcastle-Ottawa scale (NOS) was used to evaluate the quality of case-control studies. The scale was evaluated for three aspects: case selection, comparability and results. The full score was 9, and the total score of 7 or more represented high quality literature.

Statistical analysis method

RevMan 5.3 software was used for statistical analysis. The effect of count data and measurement data is represented by relative risk (RR) and weighted mean difference (MD), respectively, and the interval range of effect is estimated by 95% confidence interval (CI). Heterogeneity test was used to determine the size of heterogeneity. It was considered that the included literature was homogeneous and analysed by the fixed effect model (Mantel-Haenszel).

If I2 > 50% or p ≤ 0.1, it is considered that the included studies are not homogeneous, and the random effect model (DerSimonian-Laird) is used for analysis. If the heterogeneity is large, subgroup analysis or sensitivity analysis are used to explore the source of heterogeneity.


Inclusion of research characteristics and quality evaluation

A total of 17 studies were included in the final analysis after screening according to inclusion and exclusion criteria [4-6,10,13,16,17,20,23-25,27-32]. The flow chart of literature screening is shown in Figure 1. Among the 17 included studies, there were 3653 people who had pre-hospital or in-hospital first aid implemented, 5939 people who had routine first aid measures implemented, and 4683 (48.82%) men. All included studies concerned pre-hospital first aid, and 5 studies added hospital first aid measures on the basis of pre-hospital first aid. The quality of the included studies is high, and 13 studies belong to high-quality studies. The basic characteristics of the included studies are shown in Table I.

Emergency time

Four studies reported the time from admission to thrombolytic therapy and the time from rescue to professional treatment. The results of meta-analysis on DNT (Fig. 2A) showed that compared with conventional first aid, pre-hospital/in-hospital first aid could effectively shorten the time from admission to thrombolytic therapy (MD = –22.63, 95% CI: –27.14, 18.11, p < 0.00001). After excluding a study that only used pre-hospital emergency measures [11], the overall heterogeneity decreased from 64% to 0%, and the results were still statistically significant. The overall effect size was –24.30 (95% CI: –26.14, –22.23). Figure 2B shows the comparison results of the time from calling for help to receiving professional treatment between the two groups. Stroke patients who had pre-hospital/in-hospital first aid implemented could receive professional treatment faster (MD = –13.22, 95% CI: –18.86, –7.58, p < 0.00001). After excluding a study with low quality [28], the overall heterogeneity decreased from 91% to 41%, and the overall effect size was –9.33 (95% CI: –11.52, –7.14), the difference was statistically significant (p < 0.00001).

Emergency effect

Through the analysis of the effective rate, disability rate and mortality rate, it was found that compared with conventional emergency measures, pre-hospital/in-hospital emergency can significantly improve the effective rate (RR = 1.50, 95% CI: 1.28, 1.76, p < 0.00001; Fig. 3A), and decrease the disability rate (RR = 0.88, 95% CI: 0.80, 0.96, p = 0.004, Fig. 3B) and mortality (RR = 0.58, 95% CI: 0.49, 0.70, p < 0.00001; Fig. 4). From the subgroup analysis of results of mortality, it can be seen that compared with only pre-hospital emergency measures (RR = 0.61, 95% CI: 0.51, 0.74, p < 0.00001). The effect of pre-hospital and in-hospital emergency measures was more significant (RR = 0.38, 95% CI: 0.21, 0.68, p = 0.001). In addition, the heterogeneity analysis showed that the heterogeneity was small (0%, 0% and 46%, respectively), and the included studies had good homogeneity.


Results of central brain fever and gastrointestinal bleeding were reported in five studies. The results showed that pre-hospital/in-hospital emergency measures could reduce the incidence of central brain fever and gastrointestinal bleeding complications. Compared with conventional emergency measures, the risk of central cerebral fever in the pre-hospital/in-hospital emergency group was 0.44 (95% CI: 0.27, 0.72, p = 0.0009; Fig. 5A); and the risk of gastrointestinal bleeding was 0.44 (95% CI: 0.26, 0.73, p = 0.002; Fig. 5B).

Prognostic activities of daily living

A total of three studies reported the life ability of patients with prognosis. Compared with the conventional first aid group, the prognosis of stroke patients with pre-hospital/in-hospital emergency measures was better, and their daily living ability was improved, with the overall effect of 16.56 (95% CI: 10.78, 22.34, p < 0.00001). The results of heterogeneity analysis showed that the heterogeneity was large (I2 = 96%, p < 0.00001), and the total effect size after sensitivity analysis was still statistically significant, suggesting that the heterogeneity was relatively stable (see Fig. 6).


In our study, compared with conventional emergency measures, patients with acute stroke who received pre-hospital first aid in the hospital can significantly shorten the time from admission to thrombolytic therapy by about 22.63 minutes, and shorten the time from calling for help to receiving professional treatment by about 13.22 minutes. The results of this study suggested that the effect of effective pre-hospital and in-hospital first aid was very obvious, and the effective rate was 1.5 times that of conventional first aid. The disability rate and mortality rate of patients were lower than those of patients with acute stroke who received conventional first aid. In addition, the incidence of complications (central cerebral fever and gastrointestinal bleeding) was significantly lower than that of the control group, suggesting that pre-hospital and in-hospital emergency measures are a protective factor for patients with acute stroke. From the perspective of prognosis, the daily living ability of patients with pre-hospital and in-hospital first aid was improved, and the Barthel index was higher. As far as we know, this is the first systematic study to evaluate the effect of pre-hospital care in patients with acute stroke at home and abroad.

The results of this study are consistent with previous studies, suggesting that early emergency measures can improve the clinical results and mortality of patients with acute stroke [8,15,22]. A study of 15 subjects found that intravenous thrombolysis within 60 minutes after stroke was more likely to be discharged [7]. Studies have shown that more than 50% of the delay in the treatment time of stroke is due to the admission procedure after admission [9,26]. Therefore, shortening the time of first aid for stroke patients is crucial. Some scholars have shown that the time from admission to injection of thrombolytic drugs can be shortened about 20-30 minutes by pre-hospital notification and rapid shunt to CT scanner [11,18]. The results of this study clearly show that the reduction in treatment delay can be better achieved only by optimizing all aspects of the stroke emergency chain, although the evidence for the effectiveness of these measures is not yet clear, but thrombolysis rates in many countries indicate that more and more patients are reaching hospital within the thrombolysis time window [1]. It also provides a direction for domestic medical institutions to optimize pre-hospital and in-hospital emergency care for patients with acute stroke.

This study has certain limitations: 1) a number of original studies included are single-centre studies, and the selection of research objects and controls is not representative to a certain extent, which is prone to bias; 2) the literature data come from different regions and hospitals. There are some differences in pre-hospital and in-hospital emergency measures for acute stroke in medical centres, which cannot fully guarantee the consistency of pre-hospital and in-hospital emergency measures; 3) in addition, based on search strategies and inclusion and exclusion criteria, only two foreign studies were included in the final analysis, making the results not sufficiently representative among non-Chinese populations; 4) due to the lack of sufficient original studies, the evaluation indicators of this study are not very comprehensive, such as the lack of evaluation of onset to thrombolysis time, thrombolysis rate, patient satisfaction and prognosis of limb movement.


In summary, the results of this study show that the implementation of effective pre-hospital and in-hospital emergency measures in patients with acute stroke can shorten the time for thrombolytic therapy, indicating that early emergency treatment can be transformed into better treatment results, reduce disability rate and mortality, and improve the prognosis of patients. The results of this study suggest that the better clinical results of patients with acute stroke are related to the early implementation of emergency measures, and pre-hospital and in-hospital emergency care is worthy of wide application in clinical practice. On the other hand, based on some limitations of this study, more large-scale multi-centre studies based on different populations are needed to confirm the conclusions of this study.

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of Sandun Hospital.


The authors report no conflict of interest.

1. Audebert H, Fassbender K, Hussain MS, Ebinger M, Turc G, Uchino K, Davis S, Alexandrov A, Grotta J; PRESTO Group. The PRE-hospital Stroke Treatment Organization. Int J Stroke 2017; 12: 932-940.
2. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Das SR, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Jordan LC, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, O’Flaherty M, Pandey A, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Spartano NL, Stokes A, Tirschwell DL, Tsao CW, Turakhia MP, VanWagner LB, Wilkins JT, Wong SS, Virani SS; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation 2019; 139: e56-e528.
3. Cucchiara B, George DK, Kasner SE, Knutsson M, Denison H, Ladenvall P, Amarenco P, Johnston SC. Disability after minor stroke and TIA: A secondary analysis of the SOCRATES trial. Neurology 2019; 93: e708-e716.
4. Cheng LM, Hu ZJ, Liu XL. Application of pre-hospital emergency care in acute cerebral hemorrhage and its influence to prognosis. China Med Her 2011; 8: 176-177.
5. Chen YF, Zhang CP, Wang SN, Wang LM, Wang LQ. Application effect of pre-hospital first aid and green channel in the treatment of acute ischemic stroke. J Prev Med Chin Peopl Liber Army 2019; 37: 180-181.
6. Deng XF, Xiang L, Feng X, He QL, Zhang XL, Li XQ, Wang XJ. Construction of in-hospital thrombolysis for acute ischemic stroke. J Clin Emerg 2019; 20: 860-865.
7. Ebinger M, Kunz A, Wendt M, Rozanski M, Winter B, Waldschmidt C, Weber J, Villringer K, Fiebach JB, Audebert HJ. Effects of golden hour thrombolysis: a Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke (PHANTOM-S) substudy. JAMA Neurol 2015; 72: 25-30.
8. Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, Brott T, Cohen G, Davis S, Donnan G, Grotta J, Howard G, Kaste M, Koga M, von Kummer R, Lansberg M, Lindley RI, Murray G, Olivot JM, Parsons M, Tilley B, Toni D, Toyoda K, Wahlgren N, Wardlaw J, Whiteley W, del Zoppo GJ, Baigent C, Sandercock P, Hacke W; Stroke Thrombolysis Trialists’ Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014; 384: 1929-1935.
9. Fonarow GC, Smith EE, Saver JL, Reeves MJ, Bhatt DL, Grau-Sepulveda MV, Olson DM, Hernandez AF, Peterson ED, Schwamm LH. Timeliness of tissue-type plasminogen activator therapy in acute ischemic stroke: patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 minutes. Circulation 2011; 123: 750-758.
10. Kunz A, Ebinger M, Geisler F, Rozanski M, Waldschmidt C, Weber JE, Wendt M, Winter B, Zieschang K, Fiebach JB, Villringer K, Erdur H, Scheitz JF, Tütüncü S, Bollweg K, Grittner U, Kaczmarek S, Endres M, Nolte CH, Audebert HJ. Functional outcomes of pre-hospital thrombolysis in a mobile stroke treatment unit compared with conventional care: an observational registry study. Lancet Neurol 2016; 15: 1035-1043.
11. Köhrmann M, Schellinger PD, Breuer L, Dohrn M, Kuramatsu JB, Blinzler C, Schwab S, Huttner HB. Avoiding in hospital delays and eliminating the three-hour effect in thrombolysis
12. for stroke. Int J Stroke 2011; 6: 493-497.
13. Li W, Zhao WH, Jiang T, Zhang XZ. Application of pre-hospital emergency care intervention procedures in patients with acute cerebral hemorrhage. Mod Clin Nurs 2015; 14: 58-61.
14. Li N. Application of emergency care in pre-hospital rescue for acute stroke patients. China Med Hera 2015; 12: 134-137, 142.
15. Lan XF. Effect of nursing intervention on neurological function and life treatment of patients with acute cerebral infarction. J Clin Med Pract 2014; 18: 13-18.
16. Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, Albers GW, Kaste M, Marler JR, Hamilton SA, Tilley BC, Davis SM,Donnan GA, Hacke W; ECASS, ATLANTIS, NINDS and EPITHET rt-PA Study Group, Allen K, Mau J, Meier D, del Zoppo G, De Silva DA, Butcher KS, Parsons MW, Barber PA, Levi C, Bladin C, Byrnes G. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010; 375: 1695-1703.
17. Meng YJ. Application value of pre-hospital emergency care pathway in intervention in patients with hypertensive intracerebral hemorrhage. J Chengdu Med Coll 2019; 14: 672-675, 679.
18. Ma YH, Ji X. Effect of pre-hospital and in-hospital emergency modes on prognosis of patients with cerebral hemorrhage. Chin J Pract Nerv Dis 2016; 19: 16-18.
19. Meretoja A, Strbian D, Mustanoja S, Tatlisumak T, Lindsberg PJ, Kaste M. Reducing in-hospital delay to 20 minutes in stroke thrombolysis. Neurology 2012; 79: 306-313.
20. Marler JR, Tilley BC, Lu M, Brott TG, Lyden PC, Grotta JC, Broderick JP, Levine SR, Frankel MP, Horowitz SH, Haley EC Jr, Lewandowski CA, Kwiatkowski TP. Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study. Neurology 2000; 55: 1649-1655.
21. Shao XY. Effect of prehospital emergency nursing on prognosis of patients with acute cerebral hemorrhage. J Clin Med Pract 2015;19: 17-19.
22. Sarikaya H, Ferro J, Arnold M. Stroke prevention – medical and lifestyle measures. Eur Neurol 2015; 73: 150-157.
23. Saver JL, Fonarow GC, Smith EE, Reeves MJ, Grau-Sepulveda MV, Pan W, Olson DM, Hernandez AF, Peterson ED, Schwamm LH. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 2013; 309: 2480-2488.
24. Wang LJ, Wang N. Curative effect of intravenous thrombolysis by inside and outside of hospital emergency mode on ischemic stroke. J Kunming Med Univ 2018; 39: 114-117.
25. Wu R. Application of pre-hospital emergency nursing pathway in pre-hospital emergency of stroke patients. Mod Clin Nurs 2011; 10: 41-43.
26. Wendt M, Ebinger M, Kunz A, Rozanski M, Waldschmidt C, Weber JE, Winter B, Koch PM, Freitag E, Reich J, Schremmer D, Audebert HJ; STEMO Consortium. Improved prehospital triage of patients with stroke in a specialized stroke ambulance: results of the pre-hospital acute neurological therapy and optimization of medical care in stroke study. Stroke 2015; 46: 740-745.
27. Wahlgren N, Ahmed N, Dávalos A, Ford GA, Grond M, Hacke W, Hennerici MG, Kaste M, Kuelkens S, Larrue V, Lees KR, Roine RO, Soinne L, Toni D, Vanhooren G; SITS-MOST investigators. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007; 369: 275-282.
28. Yang J. Effect of the integrated first-aid care mode on the rehabilitation effect of elderly patients with acute cerebral infarction. Chin J Prev Control Chronic Dis 2017; 25: 548-550.
29. Zhao Y, Yuan YF, Yan YJ, Li L. Influence of pre hospital emergency intervention on onset thrombolysis time of patients with acute ischemic stroke and analysis of thrombolytic effect. J North Sichuan Med Coll 2021; 36: 762-765.
30. Zheng XL. Effect of integrated emergency nursing mode on neurological function and quality of life of patients with hypertensive cerebral hemorrhage. Henan Med Res 2019; 28: 3251-3252.
31. Zhong E. Application effect of pre-hospital emergency nursing pathway in pre-hospital emergency of stroke patients. Prac J Cardiac Cereb Pneumal Vasc Dis 2014; 22: 88-89.
32. Zhang X. Analysis of pre-hospital emergency care intervention in patients with acute cerebral hemorrhage. Chinese J Med Guide 2017; 19: 309-310.
33. Zhi SM, Fang GX, Liu LH, Yan J, Yu HY. Pre-hospital first aid for patients with acute stroke. J Clin Med Prac 2018; 22: 128-130.
Copyright: © 2022 Mossakowski Medical Research Centre Polish Academy of Sciences and the Polish Association of Neuropathologists. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2022 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.