Stroke is the leading cause of disability among adults in the United States (US) and in Europe. Nearly 800,000 new strokes occur per year in the US and 1.1 million in Europe [
Ischemic strokes (caused by in situ thrombosis, embolism, or systemic hypoperfusion) are the most common type of strokes worldwide (87%) [
Alteplase (recombinant tissue plasminogen activator or rt-PA), the only approved medical therapy for acute ischemic stroke, has been shown to be safe and effective if given within 3 hours of symptoms onset [
The utilization of thrombolytic therapy for acute stroke patients in the developing countries is low (less than 1% to 3%) compared to developed countries (up to 10%) [
To date, there is no published outcome research regarding acute stroke care in Lebanon. Our study examined the utilization of thrombolytic therapy in patients presenting with acute stroke to a tertiary care center in Beirut, Lebanon. Patient characteristics and outcomes in addition to barriers to rt-PA utilization in this setting were also described comparing the two groups (rt-PA versus No rt-PA).
The study was conducted in the Emergency department (ED) at the American University of Beirut Medical Center (AUBMC), the largest tertiary care center in Lebanon, with around 49,000 ED patient visits per year. The ED is staffed 38% of the time by American Board certified emergency medicine (EM) physicians and the rest of the time by physicians from different medical and surgical specialties. American Board certified neurologists and neurosurgeons are available for consultation 24 hours a day. Computer tomography (CT) imaging is available 24 hours of the day in the ED. The emergency medical services (EMS) agencies in Beirut are volunteer-based with Basic Life Support (BLS) level providers.
A retrospective chart analysis of adult patients who presented to the ED between June 1st 2009 and June 1st 2010 with symptoms of suspected stroke and who had a final hospital discharge diagnosis of ischemic cerebrovascular accident (CVA) was done. The study was approved by the AUB Institutional Review Board.
All adult patients (18 years and older) who presented to the ED during the study period with stroke symptoms were included if their corresponding chart had one of the following ICD-9 codes at hospital discharge: 434.00 (cerebral thrombosis without mention of cerebral infarction), 434.01 (cerebral thrombosis with cerebral infarction), 434.10 (cerebral embolism without mention of cerebral infarction), 434.11 (cerebral embolism with cerebral infarction), 434.90 (cerebral artery occlusion without mention of cerebral infarction), 434.91 (cerebral artery occlusion with cerebral infarction), 997.02 (iatrogenic cerebrovascular infarction or hemorrhage), E934.4 (adverse effects of fibrinolysis-affecting drugs), and 436 (acute but ill-defined cerebrovascular disease). Exclusion criteria were being of age <18 and missing ED charts. A total of 90 cases were reviewed. Three were excluded for missing charts. Eighty-seven patients were included in the study.
A data abstraction form was developed specifically for the purpose of this study. Charts were reviewed retrospectively and the data collected from the electronic health records included the following: patients’ demographics and characteristics, ED presentation (signs and symptoms) information, radiology and laboratory results, time intervals (symptoms onset to ED presentation, symptoms onset to rt-PA administration), rt-PA utilization contraindications to rt-PA, hospital course (surgical procedures and MRI imaging), and patient outcomes (residual symptoms at hospital discharge, SICH, mortality). Modified Rankin scale (mRs) scores were also calculated for patients based on last neurologic exam prior to discharge from hospital. Patients with a mRs score of 2 or less were considered to have a favorable neurologic outcome. Patients with scores ≥3 were considered to have poor outcome at discharge [
The Statistical Package for Social Sciences (SPSS), version 20.0, was used for data entry and analyses. Descriptive analyses were carried out by calculating the number and percent for categorical variables, whereas the mean, standard deviation (±SD), median and Interquartile Range (IQR) were calculated for continuous variables. In addition, Chi-square or Fisher’s exact test was used to compare categorical variables between rt-PA and no rt-PA groups. The 2-sample
A total of 87 patients were included in the study. These consisted of 50 males (57.5%) and 37 females (42.5%) with a mean age of 71.9 (SD = 11.8) years. Most patients arrived by private transport (85.1%). Weakness and loss of speech were the most common presenting signs (56.3%) followed by numbness (24.1%). Motor deficit was the most common physical finding (71.3%) followed by cranial nerve deficit (35.6%). The exact onset of symptoms was known in 82 patients (94.3%) with 48 patients (55.2%) presenting more than 6 hours after symptoms onset. Only 33 patients (37.9%) presented within 4.5 hours of symptom onset.
Nine patients (10.3%, 95% CI (5.5–18.5)) received rt-PA: seven intravenous (IV) and two intra-arterial rt-PA. The mean time interval from symptom onset to IV rt-PA was 193.9 min (
Time analysis for patients with IV rt-PA.
Symptoms onset to ED triage_ |
|
0–4.5 hours | 33 (37.9) |
4.5–6 hours | 6 (6.9) |
>6 hours | 48 (55.2) |
Door to CT (min) |
|
Mean (SD) | 49.4 (16.1) |
Median (IRQ) | 51.0 (43.0–61.0) |
Door to IV rt-PA (min) |
|
Mean (SD) | 102.4 (33.4) |
Median (IRQ) | 105.0 (80.0–110.0) |
Symptoms onset to IV rt-PA (min) |
|
Mean (SD) | 193.9 (42.8) |
Median (IQR) | 180.0 (150.0–240.0) |
Characteristics of patients presenting within 4.5 hours from symptom onset by group (rt-PA versus no rt-PA).
Characteristics | All | No rt-PA | rt-PA |
|
---|---|---|---|---|
Total sample |
|
|
|
|
Gender | ||||
Male | 15 (45.5%) | 12 (48.0%) | 3 (37.5%) | 0.70 |
Female | 18 (54.5%) | 13 (52.0%) | 5 (62.5%) | |
Age (mean, sd) | 70.6 (13.6) | 68.7 (14.3) | 77.7 (6.9) | 0.23 |
Arrival mode | ||||
EMS | 5 (15.2%) | 5 (20.0%) | 0 (0.0%) | 0.30 |
Private | 26 (78.8%) | 19 (76.0%) | 7 (87.5%) | |
Unknown | 2 (6.1%) | 1 (4.0%) | 1 (12.5%) | |
Presenting symptoms | ||||
Weakness | 23 (69.7%) | 18 (72.0%) | 5 (62.5%) | 0.67 |
Numbness | 6 (18.2%) | 6 (24.0%) | 0 (0.0%) | 0.30 |
Loss of vision | 2 (6.1%) | 1 (4.0%) | 1 (12.5%) | 0.43 |
Loss of speech | 24 (72.7%) | 17 (68.0%) | 7 (87.5%) | 0.39 |
Headache | 33 (100.0%) | 0 (0.0%) | 0 (0.0%) | — |
Dizziness | 2 (6.1%) | 2 (8.0%) | 0 (0.0%) | 1.00 |
Ataxia | 1 (3.0%) | 1 (4.0%) | 0 (0.0%) | 1.00 |
Decreased LOC | 9 (27.3%) | 9 (36.0%) | 0 (0.0%) | 0.07 |
Dysphagia/syncope/vertigo | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | — |
Fall | 2 (6.1%) | 2 (8.0%) | 0 (0.05) | 1.00 |
Past medical history | ||||
HTN | 28 (84.8%) | 22 (88.0%) | 6 (75.0%) | 0.57 |
Diabetes | 13 (39.4%) | 10 (40.0%) | 3 (37.5%) | 1.00 |
CAD | 9 (27.3%) | 7 (28.0%) | 2 (25.0%) | 1.00 |
CHF | 3 (9.1%) | 3 (12.0%) | 0 (0.0%) | 0.56 |
AFIB/aflutter | 7 (21.2%) | 6 (24.0%) | 1 (12.5%) | 0.65 |
Dyslipidemia | 16 (48.5%) | 12 (48.0%) | 4 (50.0%) | 1.00 |
Peptic ulcer disease/GI bleed | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | — |
CVA | 11 (33.3%) | 10 (40.0%) | 1 (12.5%) | 0.22 |
Seizure | 3 (9.1%) | 2 (8.0%) | 1 (12.5%) | 1.00 |
TIA | 3 (9.1%) | 2 (8.0%) | 1 (12.5%) | 1.00 |
ICH | 1 (3.0%) | 1 (4.0%) | 0 (0.0%) | 1.00 |
Dementia | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | — |
Cancer | 1 (3.0%) | 0 (0.0%) | 1 (12.5%) | 0.24 |
Smoking | ||||
Yes | 10 (33.3%) | 6 (27.3%) | 4 (50.0%) | 0.41 |
Previous | 7 (23.3%) | 5 (22.7%) | 2 (25.0%) | |
No | 13 (43.3%) | 11 (50.0%) | 2 (25.0%) | |
Medications | ||||
Low molecular weight heparin | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | — |
Aspirin | 16 (48.5%) | 13 (52.0%) | 3 (37.5%) | 0.69 |
Clopidogrel | 5 (15.6%) | 4 (16.7%) | 1 (12.5%) | 1.00 |
Warfarin | 5 (15.6%) | 5 (20.8%) | 0 (0.0%) | 0.30 |
Physical examination | ||||
Mental status change | 7 (21.2%) | 7 (28.0%) | 0 (0.0%) | 0.15 |
Motor deficit | 25 (75.8%) | 18 (72.0%) | 7 (87.5%) | 0.64 |
Sensory deficit | 3 (9.4%) | 3 (12.5%) | 0 (0.0%) | 0.56 |
Cranial nerve deficit | 14 (42.4%) | 9 (36.0%) | 5 (62.5%) | 0.24 |
Gait change | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | — |
Cerebellar deficit | 2 (6.1%) | 2 (8.0%) | 0 (0.0%) | 1.00 |
Babinski positive | 12 (36.4%) | 8 (32.0%) | 4 (50.05) | 0.42 |
Vital signs (mean sd) | ||||
Systolic BP | 153.0 (30.4) | 152.3 (30.0) | 156.2 (34.8) | 0.69 |
Diastolic BP | 78.0 (14.7) | 76.4 (13.9) | 84.8 (17.5) | 0.23 |
Heart rate | 83.0 (21.5) | 82.7 (22.3) | 84.5 (19.6) | 0.83 |
Blood glucose | 164.4 (82.3) | 164.7 (83.0) | 163.7 (87.3) | 0.95 |
Laboratory (mean sd) | ||||
Platelet count K | 223.9 (64.9) | 230.5 (68.4) | 195.2 (38.8) | 0.12 |
International normalized ratio (INR) | 1.2 (0.4) | 1.3 (0.4) | 1.0 (0.0) | 0.51 |
Prothrombin time (PT) | 14.9 (5.0) | 15.5 (5.3) | 11.6 (0.1) | 0.41 |
Partial thromboplastin time (PTT) | 32.0 (7.1) | 33.2 (7.5) | 27.3 (1.8) | 0.27 |
CT | ||||
CT done | 31 (93.9%) | 23 (92.0%) | 8 (100.0%) | 1.00 |
Acute infarction | 18 (54.5%) | 16 (69.6%) | 2 (25.0%) | 0.04 |
MRI | ||||
MRI done | 24 (72.7%) | 19 (76.0%) | 5 (62.5%) | 0.65 |
Acute infarction | 21 (63.6%) | 17 (89.5%) | 4 (80.0%) | 0.52 |
Physician specialty | ||||
EM | 18 (54.5%) | 12 (48.0%) | 6 (75.0%) | 0.24 |
Other |
15 (45.5%) | 13 (52.5%) | 2 (25.0%) |
Among patients presenting with acute stroke within the treatment window (<4.5 hours of symptom onset), eight patients received rt-PA (7 IV rt-PA and one intra-arterial rt-PA). An additional patient received intra-arterial rt-PA at 4.8 hours and was not included in the comparison presented in Table
Among patients who presented within the treatment window (<4.5 hrs), those who received IV rt-PA had shorter mean door to CT completion time interval (
Most patients survived to hospital discharge (90.8%) with 15 having full resolution of their deficit. Five patients died during their hospital course (5.7%) and three had SICH (3.4%). There were no significant differences in complications (SICH and mortality) or outcomes (survival to hospital discharge, resolution of deficit, and mRs scores) when comparing patients in both groups (rt-PA or No rt-PA) (Table
Outcomes of patients by Group (rt-PA versus no rt-PA).
Outcome | No-rt-PA group | rt-PA group |
|
---|---|---|---|
|
|
||
Complications | |||
None (%) | 71 (91.0) | 8 (88.9) | 0.65 |
SICH (%) | 3 (3.8) | 0 (0) | 1 |
Mortality (%) | 4 (5.1) | 1 (11.1) | 0.5 |
Resolution of deficit at discharge (%) | 14 (20.0) | 1 (12.5) | 1 |
Modified Rankin scale (mRs) score (%) | 1 | ||
Favorable outcome (Score ≤2) | 43 (58.1) | 5 (55.6) | |
Poor outcome (Score ≥3) | 31 (41.9) | 4 (44.4) | |
Discharged alive (%) | 74 (94.9) | 8 (88.9) | 0.65 |
The administration rate of rt-PA (10.3%) in our setting was higher than previously reported rates in other developing countries [
Delayed presentation was the main contraindication to rt-PA administration in our setting. More than half of the patients (55.2%) presented to ED more than 6 hours after the onset of symptoms. Although not directly addressed by our study, several factors including but not limited to poor recognition of stroke symptoms and failure to react appropriately in addition to failure to activate the EMS system (most of the patients used private transport instead of calling an ambulance) may have contributed to this delay in presentation. Studies examining barriers to rt-PA utilization in developed countries cite delayed presentation as the most important patient related barrier [
On the other hand, factors that reduce the odds of delay in presentation after acute stroke include higher stroke severity and arrival by ambulance [
The results of our study should be considered in light of its limitations. First, the sample size was small which may have affected the power to detect a statistically significant difference in short-term outcomes in both groups of patients (rt-PA versus No rt-PA). Another limitation is inherent to the retrospective nature of the study; we did not examine long-term outcomes such as disability at 3 months where thrombolysis has been shown to have most impacts since this usually requires patient followup. A third is that our data was collected from only one medical center in Beirut. We assumed this sample would be representative of the overall urban population in Beirut. The rate of rt-PA utilization in other hospitals in Beirut is different since they vary in staffing, capabilities, and services provided for patients with acute stroke. Nonetheless, the study findings highlight important issues related to acute stroke treatment in our setting, which corroborates findings from similar studies in other developing countries.
In our setting, rt-PA utilization was higher than expected. Public education regarding stroke is needed to reduce preadmission barriers to rt-PA administration, decrease time from symptoms onset to ED presentation, and potentially improve outcomes further. A larger prospective study would help delineate more clearly other areas for possible interventions to improve outcomes in patients with acute stroke.
The authors declare that there is no conflict of interests regarding the publication of this paper.