Volume 6, Issue 4 (Autumn 2020)                   Caspian.J.Neurol.Sci 2020, 6(4): 244-250 | Back to browse issues page

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Hosseininezhad M, Tabari-Khomeian R, Moaddabi Y, Ghayeghran A, Esmaeilzade S, Ghasemi M, et al . Symptom-to-needle Times in Acute Ischemic Stroke and Its Prehospital Related Factors. Caspian.J.Neurol.Sci. 2020; 6 (4) :244-250
URL: http://cjns.gums.ac.ir/article-1-366-en.html
1- Department of Neurology, School of Medicine, Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran
2- Social Determinants of Health Research Center, Guilan University of Medical Sciences, Rasht, Iran
3- General Physician, Guilan University of Medical Sciences, Rasht, Iran
4- Department of Emergency Medicine, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
5- Poursina hospital, Guilan university of Medical Sciences, Rasht, Iran
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Intravenous (IV) recombinant tissue Plasminogen Activator (rtPA) is the only Food and Drug Administration (FDA) approved pharmacological therapy for the treatment of Acute Ischemic Stroke (AIS) [1]. Only small proportions of patients with ischemic stroke receive IV-rtPA, in most centers. The most important factor limiting intravenous rtPA administration is the time because it needs to be administered within 4.5 hours of symptom onset. The clinical benefit of intravenous rtPA diminishes rapidly even during the golden time [2]. Even for the patients arriving in golden time, the administration of rtPA is not always done. Also, the contraindications for administering intravenous thrombolytic should be identified [3].

National guidelines have supported the rapid evaluation and treatment of patients with AIS. National Institute of Neurological Disorder timeline targets for attaining CT scan in 20 minutes to start rtPA infusion in 60 minutes of arrival to the Emergency Department. Currently, most hospitals struggle to have half of their AIS patients meet these targets [4].

In Iran, there has been an improvement in stroke management. However, reports suggest that the administration of IV-tPA in Iran is lower than in many other countries [5]. Therefore, the Iranian Ministry of Health has recently announced that the prevention and treatment of stroke is a national health priority [6].

This study aims to evaluate symptom to needle time and factors associated with the prehospital delay in patients with acute ischemic stroke referred to Poursina Hospital, the only stroke specialist center in the city of Rasht, northern of Iran.

Patients and Methods

In this cross-sectional study, all patients with AIS referred to Poursina Hospital, a referral hospital in the north of Iran from June to December 2016, were evaluated. The patients’ data were collected via a checklist, including demographic information (age, sex), education, occupation, place of residence, patient’s companion degree and education, chief complaints, precise onset time of symptoms, use of Emergency Medical Service (EMS), exact Emergency Department (ED) arrival time, admission time, first visit time by the physician, Computed Tomography (CT) time, and rtPA time.

The patients were divided into two groups based on their arrival at the ED within the therapeutic window (non-delayed) or arrival after that time (delayed). Outcome measures were mean symptom-to-door, door-to-admission, admission-to-doctor, doctor-to-CT, CT-to-treatment, door-to-needle, and symptom-to-needle times and determining factors associated with prehospital delays in treating acute stroke.

Patients with missing data, referred from another hospital, or with severe conditions who died before treatment were excluded. Statistical analyses were performed in SPSS v. 21. For continuous variables, Means±SD were calculated for normally distributed data. Data were analyzed using t test or Mann-Whitney U test as deemed appropriate and the Chi-square test for categorical parameters. A P-value of less than 0.05 indicated statistical significance.


A total of 530 patients with ischemic stroke were admitted during the study period. However, 208 patients were excluded due to incomplete data. Among 322 remaining patients, 179 patients (55.6%) were men and 143 (44.4%) were women. Their Mean±SD of age was 74.7±8.85) years. About 32.3% of patients were housewives, 21.1% unemployed, and 39.4% were uneducated. Also, 93.8% of the patients’ companions were first-degree relatives and 37.3% of them had a diploma. About 34.5% of patients presented with paresis and 21.4% and 15.8% presented with paresthesia and facial paresis, respectively. Besides, 31.67% of the patients lived in Rasht City and 22.9% of the patients came to ED using EMS (Table 1).


EMS was used more in the non-delayed group. According to the findings of 322 patients, only 74 (22.98%) were transferred to the hospital via EMS. Most of these patients (64.86%) were taken to the hospital at the right time and received the necessary medical care. On the other hand, of 248 patients who were transferred to the hospital with other methods of transportation, only 22 patients (8.87%) had reached the hospital at the right time. Statistical analysis showed a significant relationship between ambulance use and arriving at to hospital at the right time (P<0.001) (Table 2). Furthermore, results indicated patients with higher educational levels and with home addresses closer to ED tend to arrive earlier.


Among 322 patients, only 70 patients (21.7%) arrived at the appropriate time, and of those, 45 patients (overall:13.9%) received intravenous rtPA. Out of 25 patients arrived within the therapeutic window and did not receive rtPA, 5 patients were diagnosed with TIA, 10 patients were diagnosed with ICH; 3 patients used warfarin, 4 patients had a history of the previous stroke, and 3 patients had systolic blood pressure higher than 185 mm Hg.

We evaluated symptom to needle time in the 45 patients received rtPA. The mean onset-to-door OTD time was 105±46 (range: 15-225 min) min. The mean door-to-admission time was 3±2 (range: 1-10 min) min. The mean admission-to-doctor time was 7±8 (range: 1-50 min) min.

The mean doctor-to-CT time was 15±8 (range: 5-40) min. The mean CT-to-treatment time was 26±17 (range: 5-90 min) min. The mean door-to-treatment time was 49±23 (range: 15-125 min) min. The mean symptom-to-needle time was 152±46 (range: 50-270 min) min (Table 3).



Reports from Iran suggested that less than 30% of the stroke patients arrive at the hospital within 3 hours of onset and about 40% of the patients are not admitted to the ED on the day of symptom onset [6]. Some reports from other countries showed that 26% to 28% of the patients arrive at the ED within 2 hours of onset; nevertheless, these timings have been analyzed by different methods [7-9]. Our study showed that 70 of 322 patients (21.7%) arrived within the therapeutic window and 13.9% of patients were treated with IV rtPA, which is compatible with other studies in Iran but lower than times found in other developed countries [3, 10]. Nikkhah et al. in a study in Mashhad, Iran, on AIS patients, reported that 14.3% of the patients were admitted within the therapeutic window and only 1.2% of patients received IV-rtPA. In comparison with this study, our result is much better and a higher percentage of patients were treated with IV-rtPA [5].

The sex ratio and the mean age was similar to other studies, and we did not observe differences in sex between the two groups [3, 5, 10, 11]. In this study, 34.5%, 21.4%, and 15.8% of the patients presented with paresis, paresthesia, and facial paresis, respectively. All patients with speech disturbances arrived within the therapeutic window. On the other hand, 94% of patients with facial paresis, 92% of patients with a balance disorder, and 88% of patients with headache were in the delayed group. The reason for this delay might be due to a lack of understanding of symptom seriousness. Moreover, misinterpreting stroke symptoms can delay ED arrival [7, 12, 13].

A lower proportion of patients arrived by EMS were in the delayed group than the non-delayed group, as EMS decreases the prehospital delay by hastening the transportation and triage processes [7, 8, 14]. These results are consistent with that of Dae-Hyun Kim et al. who investigated whether EMS use and prehospital notification can shorten the time to thrombolytic therapy in a stroke. In their study, 78.5% were transported to the hospital via EMS. The patients who used EMS had shorter median onset-to-arrival time. They also showed that pre-notification by EMS was associated with shorter median door-to-imaging and door-to-needle times (DNT) [15].

Our study indicates that patients with higher levels of education arrive sooner at the hospital which is similar to other study results [16]. But Kim and colleagues showed no difference in education levels [7]. The present study showed that the longer distance to the ED, the more delay in presentation to ED, which is compatible with other reports [3]. This study indicates that unemployed status predicts delays in the presentation which is to a large extent similar to previous investigations [17].

According to Guidelines of Acute Ischemic Stroke, the conventional goal is to begin physician evaluation in less than 10 minutes, obtain CT in 20 minutes and commence rtPA infusion in 60 minutes of arrival to the ED [4].

In this study, the mean door-to-doctor time was 10±11 min, and the Mean±SD doctor-to-CT time was 15±8 min. As mentioned, the mean DNT was 49±23 min and 75.5% of the patients received rtPA in less than 60 min. In Nikkhah et al.'s study in Mashhad, the Mean±SD OTD time and to be visited by the on-call neurologist were 113.2±21.3 and 19.3±4.3 min, respectively. The Mean±SD door-to-CT scan time was 14.3±5.1 min and the Mean±SD onset-to needle and DNT were 172.1±13.1 and 57.6±8.2 min, respectively [5]. In comparison to this study, our timing is better which led to a higher percentage of patients receiving intravenous thrombolytic.

In a study in Egypt, only 5.8% of those who were eligible for receiving intravenous thrombolysis received intravenous rtPA which is to a large extent lower than our study results. Their study showed that the Mean±SD onset-to-arrival time was 147.2±42.5 min and the Mean±SD DNT was 87.5±16.4 min [18]. In comparison with the current study, they had a better arrival time even though our DNT is much better.

One study in Taiwan on patients with AIS reported that 21.8% of the patients arrived at the ED within 3 hours of stroke onset, and 5.2% received intravenous thrombolytic. Stroke code improved the number and frequency of IV-tPA treatments for patients with an OTD time of fewer than 3 hours and the efficiency of IV-tPA administration. The median DNT decreased and the percentage of DNT of less than 60 min increased [19]. Their study showed the importance of stroke code in stroke centers.

A prospective study was conducted in the United Kingdom for over 4 years, including 10556 patients. Overall, 11.4% of patients were treated with IVT and the median DNT was 54 min with 61% treated in less than 60 min from arrival at the hospital [20]. In comparison with this study, our numbers are greater. Another study in India was conducted on patients with AIS; 31.87% of patients underwent intravenous thrombolytic therapy. About 23.81% of patients had OTD of 2 h or less, 33.86% had 2-3 hours, 42.33% had 3-4.5 hours, and the median DNT was 63 min [21]. The IVT rate was higher than this study which could be due to the earlier arrival of the patients to ED.

Our result demonstrated that the most important factors limiting IVT administration in our center are prehospital factors, including patient education, occupation, place of residence, and use of EMS. This result is in line with the work of Wafkin and colleagues who reported that the main causes of prehospital onset-to-arrival delay were stroke unawareness, long travel time, incorrect beliefs, non-available neurologists, stroke onset during sleep. Also, the causes of in-hospital delays include prolonged DNT, financial restraints, minor strokes, unavailable beds, and fear of complications [18].

Based on the previous studies, the administration of rtPA in Iran is lower than that in most developed countries but similar to other developing countries [5] which could be due to the significantly lower rate of early presentation to ED in Iran. The causes of this delay could be limited public knowledge of stroke symptoms, challenging transport of the patients to ED, lack of adequate facilities, and trained personnel for AIS in small cities.Although our in-hospital timing was acceptable, Shahjoui et al. in their study in Iran, showed that improper triage, late imaging or laboratory evaluation, lack of resources in ED were factors limiting intravenous thrombolytic [6].

This study has some limitations. Some data were collected retrospectively. This study was conducted in a single medical center with a small sample size, physicians trained in stroke management, and 24-h neurology resident coverage. Thus, the generalizability of the findings may be limited. Only the frequency of each factor delaying rtPA treatment was documented but not the minutes lost. It is to be noted that in our stroke center CT scanner is sometimes down so the times measured above do not count.

Uncertainty about the symptom onset can be reduced by instructions and training for ambulance personnel. Government and medical professionals should educate the general population regarding stroke symptoms and improve cooperative EMS systems. Also, preparing an organized and comprehensive stroke program in the hospitals will improve acute stroke management in Iran. We suggest that other studies be conducted with a larger sample size in both urban and rural areas and future studies focus on prehospital and in-hospital delaying factors.


According to this study, although two-third of eligible patients were transferred to the hospital at the right time, the rate of using EMS for patient transportation is low. More studies are needed to explore this phenomenon to enable health authorities in this issue.

Ethical Considerations

Compliance with ethical guidelines

The study was approved by the Ethics Committee of the Guilan University of Medical Sciences (IR.GUMS.REC.1395.302). All study procedures were in compliance with the ethical guidelines of the Declaration of Helsinki, 2013.


This research received no specific grant from funding agencies in the public, commercial, or non-profit sectors. 

Authors' contributions

Conceptualization: Mozaffar Hosseininezhad and Seyyed Mahdi Zia Ziabari; Methodology: Rasoul Tabari-Khomeiran, Amirreza Ghayeghran, and Sedighe Esmaeilzadeh; Investigation: Mozaffar Hosseininezhad, Yaser Moaddabi, and Sedighe Esmaeilzadeh; Writing the original draft, review, and editing: Mozaffar Hosseininezhad, Rasoul Tabari-Khomeian, Yaser Moaddabi, Amirreza Ghayeghran, Sedighe Esmaeilzade, Seyyed Mahdi Zia Ziabari, and Maryam Ghasemi; Resources: Rasoul Tabari-Khomeian, Sedighe Esmaeilzade, and Maryam Ghasemi; Supervision: Mozaffar Hosseininezhad, Seyyed Mahdi Zia Ziabari, and Amirreza Ghayeghran.

Conflict of interest

The authors declared no conflicts of interest.


The authors express their gratitude to the heads of the Neurology Department of Poursina Hospital and Research Deputy of Guilan University of Medical Sciences.



1.Mowla A, Doyle J, Lail NS, Deline C, Ching M, Crumlish A, et al. Delays in door-toneedle time for acute ischemic stroke in the emergency department: A comprehensive stroke center experience. Neurology. 2017; 88(Suppl 16):102-5. https://n.neurology.org/content/88/16_Supplement/P4.273.short

2.Kruyt ND, Nederkoorn PJ, Dennis M, Leys D, Ringleb PA, Rudd AG et al. Door-to-needle time and the proportion of patients receiving intravenous thrombolysis in acute ischemic stroke: Uniform interpretation and reporting. Stroke. 2013; 44(11):3249-53. [DOI:10.1161/STROKEAHA.113.001885] [PMID]

3.Hong ES, Kim SH, Kim WY, Ahn R, Hong JS. Factors associated with prehospital delay in acute stroke. Emerg Med J. 2011; 28(9):790-3. [DOI:10.1136/emj.2010.094425] [PMID]

4.Louis ED, Mayer SA, Rowland LP, Merritt HH. Merritt’s neurology. 13th edition. Philadelphia: Lippincott Williams & Wilkins; 2016. 

5.Nikkhah K, Avan A, Shoeibi A, Azarpazhooh A, Ghandehari K, Foerch C, et al. Gaps and hurdles deter against following stroke guidelines for thrombolytic therapy in Iran: Exploring the problem. J Stroke Cerebrovasc Dis. 2015; 24(2):408-15. [DOI:10.1016/j.jstrokecerebrovasdis.2014.09.012] [PMID]

6.Shahjouei S, Bavarsad-Shahripour R, Assarzadegan F, Rikhtegar R, Mehrpour M, Zamani B, et al. Acute management of stroke in Iran: Obstacles and solutions. Iran J Neurol. 2017; 16(2):62. http://ijnl.tums.ac.ir/index.php/ijnl/article/view/1148

7.Kim HJ, Ahn JH, Kim SH, Hong ES. Factors associated with prehospital delay for acute stroke in Ulsan, Korea. J Emerg Med. 2011; 41(1):59-63. [DOI:10.1016/j.jemermed.2010.04.001] [PMID]

8.Maestroni A, Mandelli C, Manganaro D, Zecca B, Rossi P, Monzani V, et al. Factors influencing delay in presentation for acute stroke in an emergency department in Milan, Italy. Emerg Med J. 2008; 25(6):340-5. [DOI:10.1136/emj.2007.048389] [PMID]

9.Morris DL, Rosamond W, Madden K, Schultz C, Hamilton S. Prehospital and emergency department delays after acute stroke: The genentech stroke presentation survey. Stroke. 2000; 31(11):2585-90. [DOI:10.1161/01.str.31.11.2585] [PMID]

10.Van Schaik SM, Scott S, de Lau LM, Van den Berg-Vos RM, Kruyt ND. Short door-to-needle times in acute ischemic stroke and prospective identification of its delaying factors. Cerebrovasc Dis Extra. 2015; 5(2):75-83. [DOI:10.1159/000432405] [PMID] [PMCID]

11.Iglesias-Mohedano A, García-Pastor A, Vázquez-Alen P, Vázquez-Alen P, Diaz-Otero F, Villanueva-Osorio JA, et al. Factors associated with in-hospital delays in treating acute stroke with intravenous thrombolysis in a tertiary centre. Reply to a letter. Neurología. 2017; 4(32):274. [DOI:10.1016/j.nrl.2015.07.004] [PMID]

12.Lacy CR, Suh D-C, Bueno M, Kostis JB. Delay in presentation and evaluation for acute stroke: Stroke Time Registry for Outcomes Knowledge and Epidemiology (S.T.R.O.K.E). Stroke. 2001; 32(1):63-9. [DOI:10.1161/01.str.32.1.63] [PMID]

13.Williams LS, Bruno A, Rouch D, Marriott DJ. Stroke patients’ knowledge of stroke: Influence on time to presentation. Stroke. 1997; 28(5):912-5. [DOI:10.1161/01.str.28.5.912] [PMID]

14.Inatomi Y, Yonehara T, Hashimoto Y, Hirano T, Uchino M. Pre-hospital delay in the use of intravenous rt-PA for acute ischemic stroke in Japan. J Neurol Sci. 2008; 270(1-2):127-32. [DOI:10.1016/j.jns.2008.02.018] [PMID]

15.Kim DH, Nah HW, Park HS, Choi JH, Kang MJ, Huh JT, et al. Impact of prehospital intervention on delay time to thrombolytic therapy in a stroke center with a systemized stroke code program. J Stroke Cerebrovasc Dis. 2016; 25(7):1665-70. [DOI:10.1016/j.jstrokecerebrovasdis.2016.02.011] [PMID]

16.Keskin Ö, Kalemoğlu M, Ulusoy RE. A clinic investigation into prehospital and emergency department delays in acute stroke care. Med Princ Pract. 2005; 14(6):408-12. [DOI:10.1159/000088114] [PMID]

17.Leung LY, Caplan LR. Factors associated with delay in presentation to the hospital for young adults with ischemic stroke. Cerebrovasc Dis. 2016; 42(1-2):10-4. [DOI:10.1159/000443242] [PMID]

18.Bahnasy WS, Ragab OAA, Elhassanien ME. Stroke onset to needle delay: Where these golden hours are lost? An Egyptian center experience. eNeurologicalSci. 2019; 14:68-71. [DOI:10.1016/j.ensci.2019.01.003] [PMID]

19.Chen CH, Tang SC, Tsai LK, Hsieh MJ, Yeh SJ, Huang KY, et al. Stroke code improves intravenous thrombolysis administration in acute ischemic stroke. PLoS One. 2014; 9(8):e104862. [DOI:10.1371/journal.pone.0104862] [PMID]

20.McVerry F, Hunter A, Dynan K, Matthews M, McCormick M, Wiggam I, et al. Country-wide analysis of systemic factors associated with acute ischemic stroke door to needle time. Front Neurol. 2019; 10:676. [DOI:10.3389/fneur.2019.00676] [PMID]

21.Khurana D, Das B, Kumar A, Kumar SA, Khandelwal N, Lal V, et al. Temporal trends in intravenous thrombolysis in acute ischemic stroke: experience from a tertiary care center in India. J Stroke Cerebrovasc Dis. 2017; 26(6):1266-73. [DOI:10.3389/fneur.2019.00676] [PMID]

Type of Study: Research | Subject: Special
Received: 2020/12/23 | Accepted: 2020/12/20 | Published: 2020/12/20

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