Assessment of onset-to-door time in acute ischemic stroke and factors associated with delay at a tertiary care center in South India

INTRODUCTION

In 2019, stroke was the second leading cause of death (11.6% of total deaths) and the third leading cause of the disability-adjusted life years (5.7% of total DALYs) globally.^[1] The number of incident stroke cases in India in 2019 was 1.29 million, and the number of deaths was 699000. It was the largest contributor to the total neurological disorder DALYs (37.9%).^[2]

The National Institute of Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator (rtPA) trial showed that patients who received alteplase were 30% more likely to have better outcomes at 3 months on assessment scales (global odds ratio for a favorable outcome was 1.7; 95% confidence interval [CI]: 1.2–1.6).^[3] The Third International Stroke Trial-3 demonstrated that treatment with intravenous tPA within 1.5 h of last-seen-well was associated with a favorable outcome at 3 months compared with placebo with an odds ratio of 2.81 (95% CI, 1.75–4.50).^[4] Most studies in the published literature have focused on factors affecting door-to-needle time and on devising strategies to decrease it. However, patients with acute ischemic stroke do not even reach the hospital within the window period and, hence, miss the opportunity of becoming eligible for thrombolysis. Hence, the time taken from symptom onset to arrival at the hospital is an important area for intervention.

Hence, we initiated this single-center study to assess the time taken from the onset of symptoms to arrival at the emergency department and look into the factors causing the pre-hospital delay.

MATERIALS AND METHODS

OBSERVATIONS AND RESULTS

The study consisted of 153 participants who presented with acute ischemic stroke to the emergency department of the tertiary care hospital; of which 90 were male (58.8%) and 63 were female (41.2%). The mean age was 62.88 ± 13.59 years (median-64 years).

Demographic and clinical profile of patients

Demographic and clinical data of the study population are summarized in Table 1. The mean OTD time was 674.33 ± 812.713 min (median: 300; interquartile range: 151–885). Out of 153, 101 (66.0%) patients were late arrivers and came after 3.5 h [Figure 1]. 15.7% of patients received thrombolysis. Other salient data is represented pictorially in Figures 2-9.

Table 1: Demographic and clinical variables of the study participants.

Age	62.88±13.59a
≤45 years	17 (11.1)b
>45 years	136 (88.9)b
Gender
Male	90 (58.8)b
Female	63 (41.2)b
Distance from onset to hospital	34.84±25.8a
≤40 km	100 (65.4)b
>40 km	53 (34.6)b
NIHSS
≤15	110 (71.9)b
>15	43 (28.1)b
Marital status
Married	143 (93.5)b
Single	10 (6.5)b
Financial status
High SES	26 (17.0)b
Middle SES	17 (11.1)b
Low SES	110 (71.9)b
Place of stroke onset
Home	129 (84.3)b
Office/Workplace	10 (6.5)b
Road	9 (5.9)b
Out-patient setting	4 (2.6)b
Chronic health-care facility	1 (0.7)b
Education
≤12th grade	142 (92.8)b
>12th grade	11 (7.2)b
Mode of living
Alone	14 (9.2)b
Family	137 (89.5)b
Friends	2 (1.3)b
Place of residence
Rural	86 (56.2)b
Urban	67 (43.8)
Visit to a local hospital
Yes	127 (83.0)b
No	26 (17.0)b
Time of onset
Day	119 (77.8)b
Night	34 (22.2)b
Day of onset
Weekday	143 (95.4)b
Weekend	10 (6.5)b
Onset-to-door time	674.33±812.713a
Early arrivers	52 (34.0)b
Late arrivers	101 (66.0)b
Previous history of stroke
Present	28 (18.3)b
Absent	125 (81.7)b
Family history of stroke
Present	25 (16.3)b
Absent	128 (83.7)b
Stroke territory
Anterior	132 (86.3)b
Posterior	21 (13.7)b
Bystander at onset
Family member	105 (68.6)b
Friend	8 (5.2)b
Colleague	6 (3.9)b
Stranger	6 (3.9)b
Alone	25 (16.4)b
Health professional	2 (2.0)b
Recognition of stroke
Yes	39 (25.5)b
No	114 (74.5)b
Perceived symptoms as serious
Yes	109 (71.2)b
No	44 (28.8)b
Knowledge about thrombolysis
Yes	6 (3.9)b
No	147 (96.1)b
Mode of transport
Ambulance	101 (66.0)b
Auto	26 (17.0)b
Own	24 (15.7)b
Vehicle taxi	2 (1.3)b

aMean±Standard Deviation; ^bn (%). NIHSS: National Institutes of Health Stroke Scale, SES: Socioeconomic status

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Figure 1:

Proportion of patients arriving within 3.5 h.

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Figure 2:

Symptoms of patients.

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Figure 3:

Risk factors for acute ischemic stroke in patients. AF: Atrial fibrillation, CAD: Coronary artery disease, TIA: Transient ischemic attack

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Figure 4:

Sources of stroke knowledge.

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Figure 5:

Proportion of patients who recognized stroke.

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Figure 6:

Proportion of patients who perceived symptoms as serious.

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Figure 7:

Mode of transport.

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Figure 8:

Number of institutions visited.

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Figure 9:

Division of onset-to-door time.

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DISCUSSION

Our study population had a median OTD time of 5 h. There seems to be an improvement in pre-hospital delay compared to the 2012 study conducted in Calicut, Kerala, where the median OTD time was 12 h.^[6] The shorter delay may have been made possible by increased availability and use of ambulance services. 66% of our patients used emergency medical services (EMS) compared to 29% in the previous study. The OTD time of 5 h is also lesser than that recorded in the study conducted in Coimbatore in the neighboring state of Tamil Nadu with a median delay of 9.5 h.^[7] However, 66% of the patients still arrived after 3.5 h. Among this, 17% of patients presented to the emergency department after 24 h. This is high compared to Western countries where 50–70% of patients arrive within 3 h, and the median OTD time is 1–2.5 h.^[8-11]

The most significant factors associated with pre-hospital delay in the multivariate analysis were the perception of symptoms as serious and delay in reaching due to traffic.

Failure to recognize stroke was associated with delay in many previous studies.^[8,12] We found that 25.5% of patients recognized stroke, which is low compared to 70–75% in developed countries and another study in North Kerala.^[7] Only 8 had knowledge about the warning symptoms of a stroke.

However, 71.2% of the study participants felt that their symptoms were serious, and this was a significant factor in early arrival.

A higher NIHSS score was seen to be associated with early arrival. This is due to an increased sense of urgency as evidenced by the fact that 80% of patients with the NIHSS scores >15 felt their symptoms were serious.

Only 3.9% of patients had knowledge about thrombolysis, which is lower than 18% in the Coimbatore study and Western countries.^[8-11] None of the participants knew about the stroke helpline number, even among those who have had a stroke before, and this points to an underwhelming effort at stroke education. A study from Iran showed that the median OTD time was 2 h when the stroke helpline number was called.^[13] Prenotification to the stroke team in the hospital was also associated with reduced in-hospital delay in previous studies.^[12,14,15] A 11% decrease in door-to-needle time was documented when prenotification was implemented.^[15]

A major cause of late arrival in the univariate analysis was a visit to a local hospital. This was documented in many previous studies as well.^[7,8] Only 17% of general practitioners are aware of the window period of thrombolysis according to a study from Tamil Nadu.^[15] There is also a lack of knowledge about stroke-ready hospitals among both patients and doctors. 5.2% of patients visited 3 institutions. This highlights the importance of increasing awareness about stroke centers in the state.

Stroke was not diagnosed in 19.7% of patients visiting a local hospital. This points to a need to increase awareness about the symptoms of stroke, especially posterior circulation stroke.

Those living in rural areas were found to arrive late in our study. This was seen in other studies as well.^[7] Patients from rural areas were seen to have lesser urgency about their symptoms compared to urban areas. 60.6% of patients who visited a local hospital also belonged to rural areas. This signifies a need to pay special attention to rural areas with respect to stroke education. The presence of risk factors did not seem to decrease pre-hospital delay, which signifies a need to educate this high-risk population.

However, we found that neither previous history of stroke nor a family history led to early arrival, which was also seen in the other studies.^[16] This suggests a disconnection between knowledge and action. Zock et al. found that recognition of stroke was not followed immediately by help-seeking behaviors. Personal experiences of spontaneous improvement were one reason for the wait-and-see strategy. This study also showed that most participants were not interested in stroke education unless they had a stroke themselves.^[17] Another study also found that 59% of patients waited for symptoms to resolve spontaneously.^[18]

Ambulance services were utilized by 66% of the population, which is greater than that reported in the 2012 Calicut study and is comparable to Western countries with a utilization rate of 60–70%.^[6,7,9-11]

The use of EMSs has been well-documented to increase the odds of early arrival in previous studies.^[9-11] Although we observed a decreased OTD time in patients using ambulance services compared to those using auto, it did not produce a significant difference in arrival within 3.5 h. This is probably because most patients coming by auto live nearer to the hospital, and those living far away, use auto to visit a local hospital before finally reaching by ambulance.

However, decreased OTD time in patients using ambulance services (median 4 h) is significant since previous studies have shown that there are improved functional outcomes with early arrival irrespective of reperfusion therapy.^[19] Delay in reaching due to traffic was also significantly associated with using auto as the mode of transport.

A previous study had observed that older age and female sex were associated with a shorter OTD; however, we found no correlation.^[7] The presence of hemiparesis also led to shorter OTD due to the increased sense of urgency. Patients with coronary artery disease were found to arrive early, which seems to be due to the increased awareness about cardiac disease in this group.

Unlike in Western countries where living alone was an important factor leading to pre-hospital delay, the mode of living did not seem to influence OTD in our study.^[11] However, being alone at the onset was found to be associated with decreased urgency and late arrival.

Stroke onset at one’s office or workplace was found to be associated with early arrival. This is probably due to the presence of one’s colleague as the bystander. Family members were seen to be more dismissive of patients’ symptoms. However, in a study conducted in Nepal, onset at home was found to lead to early arrival.^[20]

In our study, education more than 12^th grade was associated with greater recognition of stroke; however, this did not equate to early arrival.

Similar causes for pre-hospital delay were found in other studies conducted in India.^[6,7] This calls for a comprehensive stroke education campaign to improve patients’ opportunities to avail of definitive treatment, including thrombolytic therapy and mechanical thrombectomy.

CONCLUSION

Our study highlights that onset to door time delay continues to be a major hindrance to ischemic stroke patients receiving thrombolysis. Awareness campaigns focusing on thrombolysis and stroke centers among general public and primary care physicians along with improvement in ambulance services are essential to address this lacuna in stroke care in India.