Prevalence and factors influencing pre-hospital delays in patients with acute stroke

Introduction

Stroke is a serious medical concern worldwide; in 2016, the World Health Organization reported that stroke ranked as the second leading cause of death and the third leading cause of disability (1). The annual mortality rate of stroke is 5.4 million (2). According to a report in 2019 by the Ministry of Public Health in Thailand, stroke is the leading cause of death in Thailand with more than 30,000 deaths per 100,000 cases of stroke annually (3). Furthermore, a recent epidemiological stroke study in Thailand showed that the prevalence of stroke was 1.88% in populations aged 45 and above (4).

Stroke can be classified into two categories, ischemic stroke and hemorrhagic stroke (5). Ischemic stroke occurs due to a blockage of blood supply to the brain caused by atherosclerosis or thrombotic or embolic occlusion of a cerebral artery; whereas hemorrhagic stroke is caused by a ruptured blood vessel or an abnormal vascular structure (5). Ischemic stroke is the most common type of stroke, accounting for about 80% of all stroke cases (6,7). The current standard treatment for acute ischemic stroke, intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) administered within 4.5 hours of symptom onset, has been proven safe and effective in preventing death and reducing long term disability (8-10). However, the efficacy of thrombolytic treatment depends on the time and exposure to medication after symptom onset (11,12).

In the United States, several studies revealed that only a small number of patients with acute ischemic stroke received rt-PA (13-17). In Thailand, some studies showed that only 3.8–5.5% of the patients with ischemic stroke received rt-PA (18,19). Notably, pre-hospital delay is one of the major factors that reduce the proportion of acute stroke patients who receive recanalization therapies (20,21).

Pre-hospital delay comprises two different components; first, the delay from the onset of disease to the recognition of the warning signs of acute stroke, and second, the delay from the recognition of stroke warning signs to hospital arrival. Typically, a greater proportion of acute stroke patients arrive at the hospital later, with 37% to 75% arriving within 6 hours, while only 23% to 46% arrive at the hospital within the first 3 hours (22-32). Furthermore, studies have reported that the proportion of pre-hospital delays among acute stroke patients in Thailand ranges from 38.2% to 48.4% (32-34). There have been many studies conducted in different countries on the hospital arrival time and its associated factors. These studies showed that pre-hospital delays among acute stroke patients are related to the National Institute of Health Stroke Scale (NIHSS) scores, mode of transportation to the hospital, patient age, symptom progression, patient’s knowledge of stroke, and wake-up or unknown-onset stroke (22-34). Although there are many studies on pre-hospital delays among acute stroke patients, there are few studies that explore factors associated with early arrival at the hospital (within 4.5 hours of the onset of symptoms) in Thailand. Therefore, this study was conducted to provide further evidence regarding the variables associated with pre-hospital delays among patients hospitalized with acute ischemic stroke. The results of this study may facilitate people to seek timely medical treatment.

The aim of this study was to identify the factors influencing pre-hospital delays among acute stroke patients in Thailand. We present this article in accordance with the STROBE reporting checklist (available at https://jphe.amegroups.com/article/view/10.21037/jphe-24-30/rc).

Methods

Study design and setting

A retrospective study was conducted in the emergency department of Songklanagarind Hospital between 1 January 2014 and 31 December 2018. Songklanagarind Hospital is a tertiary care hospital, affiliated with the Faculty of Medicine, Prince of Songkla University, located in Hat Yai, Songkhla Province, Thailand.

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). This study was conducted with approval from the Ethics Committee of the Faculty of Medicine of Prince of Songkla University (REC 62-343-9-7). The individual consent for this retrospective analysis was waived.

Subjects

We collected data from medical records of patients aged ≥15 years who arrived at the Emergency Department of Songklanagarind Hospital within 24 hours following the onset of symptoms of acute stroke, from 1 January 2014 to 31 December 2018. The exclusion criteria were patients with in-hospital stroke or a lack of initial signs or symptoms of acute stroke. Diagnosis of acute stroke was confirmed by neuroimaging including computed tomography and magnetic resonance imaging.

Sample size

The calculation of the sample size uses the formula for estimating the proportion of an infinite population, which is based on research conducted by Wongwiangjunt et al. (34) Their findings revealed that 38.2% of acute stroke patients arrived at the emergency room within 4.5 hours after the onset of the disease. With a precision of 5% from the standard deviation, the calculation yielded a minimum required sample size of 364.

Data collection

The following data were obtained from patient medical records: demographic data including age, gender, underlying disease, and health insurance, initial signs and symptoms of acute stroke, location of symptom occurrence, mode of transportation to the hospital, type of stroke, time of onset of stroke symptoms, wake-up stroke, and stroke severity, which was calculated using the NIHSS. Based on the total score on the NIHSS, participants were classified into three groups: mild (1–4 points), moderate (5–15 points), and severe (16–42 points). Regarding the time of symptom onset at presentation to the hospital, the participants were classified into two groups, early (≤4.5 hours) and delayed (>4.5 hours) arrival to the hospital, based on the current standard treatment of acute ischemic strokes, which reported that intravenous thrombolysis therapy with rt-PA is safe and effective if administered within 4.5 hours of symptom onset (8-10). Regarding the mode of transportation to the hospital, the participants were categorized into three groups including ambulance, private transport (car, taxi, or motorcycle), and public services (social service vehicle, police car, or unknown).

Data management and analysis

Data analyses were performed using R program (R Core Team 2017, Vienna, Austria). Categorical data were presented in percentages. Continuous data were presented as mean ± standard deviation or median and interquartile range (IQR). The comparison of baseline characteristics between early and delayed arrival to the hospital groups were performed using Chi-squared test, Fisher’s exact test, Mann-Whitney U, or t-test. We conducted logistic regression analysis to evaluate the hazard ratio (odds ratio) and 95% confidence interval for testing the associations between the various factors and the delayed arrival to the hospital. A P value of less than 0.05 was considered statistically significant.

Results

Patient characteristics

From 1 January 2014 to 31 December 2018, the emergency room treated 4,000 stroke patients. We used simple random sampling and the inclusion criteria to select patients, resulting in a sample of 871 patients. Upon applying the exclusion criteria, we found that 490 patients met these criteria. After excluding these patients, we were left with a final count of 381 patients, as shown in Figure 1. The baseline characteristics of the participants are shown in Table 1. Data showed that most of the participants were male (56.4%) and the median age was 66 years. Among the participants, 40 (10.5%) had wake-up stroke. Hemiplegia and hemiparesis were the most common initial symptoms of acute stroke (n=282, 74.0%), followed by facial palsy or numbness (n=153, 40.2%). The median NIHSS score was 4 points (IQR, 2, 9 points); thus, most participants were classified into the mild severity group. Regarding the type of stroke, 193 (50.7%) had ischemic stroke, 93 (24.4%) had hemorrhagic stroke, and 33 (8.7%) had transient ischemic stroke. The most common underlying disease of the participants was hypertension (n=217, 57.0%). Regarding mode of transportation to the hospital, 293 (76.9%) of the participants arrived at the hospital via private vehicles. A total of 26 (6.8%) were referred from other hospitals.

Figure 1 Flow diagram of study participants.

Baseline characteristics according to hospital arrival time

The baseline characteristics were compared according to hospital arrival time. Between the early arrival time group and the delayed arrival time group, there was a significant difference in wake-up stroke, new-onset headache, NIHSS score, and referral from other hospitals (Table 1).

The prevalence of pre-hospital delays following acute stroke onset (>4.5 hours) was 45.7%. Hospital arrival time ranged between 9 minutes and 24 hours among acute stroke patients. The median hospital arrival time was 4 hours (IQR, 1.8, 9.3 hours). Of the 381 participants, 143 (37.5%) arrived at the hospital within 3 hours of symptom onset, 64 (16.8%) arrived between 3 and 4.5 hours, 34 (8.9%) arrived between 4.5 and 6 hours, and 140 (36.7%) arrived later than 6 hours after symptom onset.

The logistic regression analysis performed to evaluate the association between various parameters and delayed hospital arrival time is shown in Table 2. In the univariate model, delayed hospital arrival time was significantly associated with wake-up stroke, new-onset headache, and referral from other hospitals, whereas NIHSS score and stroke severity (moderate and severe) were associated with early hospital arrival time. Furthermore, in the multivariate model, the delayed hospital arrival time was also significantly associated with new-onset headache, wake-up stroke, and referral from other hospitals, while stroke severity (moderate and severe) and using an ambulance to arrive at the hospital were significantly associated with early hospital arrival time, as shown in Table 3.

Discussion

In this cross-sectional study, we found that the observed prevalence of pre-hospital delays following acute stroke onset was 45.7%. Our finding of delayed hospital arrival time is consistent with those reported in previous studies. Fladt et al. (22) reported that the prevalence of pre-hospital delays (>4.5 hours) was 42%, Song et al. (35) showed that 55.5% of the patients arrived at the hospital later than 4.5 hours following acute ischemic stroke onset, Terecoasă et al. (36) reported that 68.4% of acute ischemic stroke patients arrived at the hospital more than 4.5 hours after onset, and Revathi et al. (37) showed that prehospital delay was observed in 73.3% of acute stroke patients in South India. Furthermore, the results of the studies that investigated the prevalence of delayed hospital arrival time among acute stroke patients in Thailand are in line with those of our study. Muengtaweepongsa et al. (33) and Wannarong et al. (32) reported that 50.8% and 48.4% of the patients, respectively, arrived at the hospital later than 4.5 hours following the onset of ischemic stroke. Additionally, Wongwiangjunt et al. (34) reported that the proportion of acute stroke patients that arrived at the emergency room later than 4.5 hours after onset was as high as 61.8%. Regarding hospital arrivals at 3 and 6 hours following stroke onset, our results are consistent with those reported in previous studies in which the prevalence of hospital arrival 3 and 6 hours following stroke onset ranged from 9% to 46% and 37% to 75%, respectively (22-32,38-41). Furthermore, the median arrival time is reported to range from 2.5 to 6 hours in Western countries and from 4.25 to 15 hours in Asian countries (22,28-32,35,42-45). Based on these results, Western populations may tend to arrive earlier following stroke onset than Asian populations. This may be due to the differences in ambulance transportation and the knowledge and awareness of stroke (44,46,47).

The results of this study also revealed that pre-hospital delays were significantly associated with new-onset headache, wake-up stroke, and referral from other hospitals. Additionally, arriving at the hospital using an ambulance and stroke severity (moderate and severe) were significantly associated with an early hospital arrival time. Our results are also in concordance with previous studies, which indicate that wake-up stroke or nocturnal onset stroke was associated with a longer arrival time (35,37,42,45,48-50). In addition, referral from other hospitals was correlated with a delayed arrival time to the hospital (31,38,44,48). This might be due to traffic problems, and the long distance and travel time to reach the referred hospital. Regarding the initial symptoms of acute stroke, our study suggested that new-onset headache was associated with pre-hospital delay. However, no other presenting symptoms were associated with the arrival time. Many previous studies have shown that impaired consciousness and seizures were correlated with early hospital arrival (28-32,45,48). This may reflect the suboptimal public awareness regarding knowledge of stroke symptoms and detection among Thai people.

Concerning stroke severity, many studies have shown that greater stroke severity defined by a higher NIHSS score was associated with an early arrival time (27-30,32,34-36,38,44), which is similar to our result. Consistent with prior literature from other studies (25-27,29-31,35,39,44,45), our study suggests that the use of ambulance transportation was correlated with a shorter arrival time. However, the studies that investigated the hospital arrival time among acute stroke patients in Thailand did not show a relationship between the use of ambulance transportation and early hospital arrival (32,33). This may be due to differences in the rate of ambulances used between different hospitals and areas in the country.

Limitations

The strength of this study is that we examined a multitude of factors that may be associated with delayed hospital arrival time among acute stroke patients in Thailand. Moreover, this is the first study to evaluate the correlation between place where stroke occurred and hospital arrival time. Our study had several limitations. First, since this study was performed in a single tertiary referral center located in an urban area, findings cannot be generalized to rural areas of the country. Second, as the study design was retrospective in nature, some factors known to affect hospital arrival time, including socioeconomic status, education, and stroke knowledge and awareness were not investigated in the current study.

Conclusions

The prevalence of pre-hospital delays following acute stroke was high in Thai stroke patients. The factors associated with pre-hospital delays included: new-onset headache, wake-up stroke, and referral from other hospitals. Moreover, the use of ambulance transportation and moderate and severe strokes were associated with early hospital arrival. Our findings implicate the importance of a national stroke strategy to improve community awareness of the early symptoms of stroke and increase the use of ambulance services to promote early hospital arrival and improve stroke outcomes. Further research should be conducted using an experimental design to better determine effective interventions for improving hospital arrival time following acute stroke onset.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jphe.amegroups.com/article/view/10.21037/jphe-24-30/rc

Data Sharing Statement: Available at https://jphe.amegroups.com/article/view/10.21037/jphe-24-30/dss

Peer Review File: Available at https://jphe.amegroups.com/article/view/10.21037/jphe-24-30/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jphe.amegroups.com/article/view/10.21037/jphe-24-30/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). This study was conducted with approval from the Ethics Committee of the Faculty of Medicine of Prince of Songkla University (REC 62-343-9-7). The individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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