More than 20 years have passed since the birth of thrombolysis. Subsequent research was done in different countries and different nationalities -all geared towards reducing long-term disability with the least complications. With increasing life expectancy and lifestyle changes, the burden of stroke is rising. The majority of stroke burden is in developing countries, comprising 75.2% of deaths and 81% of DALYs (Suwanwela & Poungvarin, 2016). In the Philippines, stroke is the second leading cause of death (after cardiac disease) with a prevalence rate of 0.9%, and ranks fifth among specific diseases with the greatest burden (Unknown Author, 2014).

Emergency management of AIS is focused on attaining vascular reperfusion as soon as possible, without risking the patient's safety, most commonly with intravenous tissue plasminogen activator (tPA) (Lees et al., 2016). The benchmark study organized by the National Institute of Neurological and Communicative Disorders and Stroke (NINDS) provided evidence of benefit later from intravenous rtPA given within 3 hours, led to improved clinical outcome at 3 months at the expense of a 6% risk of symptomatic intracerebral hemorrhage (sICH) ("Tissue Plasminogen Activator for Acute Ischemic Stroke.," 1995). In the ECASS III trial, a benefit was seen for tPA administration within the 3 to 4.5 hour range, however with some exclusions (Hacke et al., 2008). In the International Stroke Trial (IST3), benefits did not diminish among patients more than 80 years old who underwent thrombolysis (Sandercock et al., 2012). Due to sICH, the Japan Alteplase Clinical Trial or J-ACT administered rTPA at a lower dose of 0.6mg/kg to Japanese patients and resulted in clinical efficacy and safety that are compatible with data reported in North America and European Union for 0.9mg/kg dose (Yamaguchi et al., 2006). In 2016, the Enhanced Control of Hypertension and Thrombolysis in Stroke Disease (ENCHANTED) trial, an open-labeled clinical trial involving predominantly Asian patients with acute ischemic stroke within 4.5 hours, did not show the noninferiority of low-dose alteplase (0.6mg/kg) to standard-dose alteplase (0.9mg/kg) concerning death and disability at 90 days. However, there were significantly fewer symptomatic intracerebral hemorrhages with low-dose alteplase (Anderson et al., 2016). Although outcome at 3 months had been the standard timeline, a few studies on short-term outcomes show that stroke patients given rTPA are more likely to be discharged directly home after hospitalization. The favorable outcome modified Rankin Scale (MRS) (MRS 2 and below) at the time of hospital discharge is significantly associated with lower NIHSS values at admission (Ifejika-Jones et al., 2011).

Intravenous rTPA is an approved cure for acute stroke with favorable short-and long-term outcomes. Although approved in the country in 1999, it was in 2016 when rTPA was available in the institution, and since then, is readily administered to eligible candidates. However, the outcomes of thrombolysis among the Filipino population remain to be seen and have been approached cautiously. A retrospective study done in the Philippines revealed good outcomes of MRS 0 to 2 on discharge (51.1%) and at 3 months (73.1%). However, in-hospital mortality was high at 14.6% (Navarro et al., 2018). Our study aims to determine the short-term outcomes and complications of acute ischemic stroke patients given rTPA in our institution. Furthermore, it aims to determine the association of MRS on discharge and the following: age, stroke etiology, stroke severity, and adverse events (hemorrhagic conversion, extracranial bleeding, orolingual edema).

The study is a retrospective observational cross-sectional study of acute ischemic stroke patients given rTPA in a government tertiary center, from January 2016 to January 2019. Inclusion criteria: (1) > 18 years old (2) clinical diagnosis of ischemic stroke (3) computed tomography (CT) or magnetic resonance imaging (MRI) indicating no intracranial hemorrhage. Exclusion criteria: (1) final diagnosis is a stroke mimicker (2) documented outcome parameter is incomplete (3) transfer to another institution (4) MRS 3 and above for post stroke patients. This study utilized total enumeration, involving the entire population of all stroke patients, resulting in a sample size of 1939.

Charts and medical records of enrolled patients were reviewed. The demographic profile, baseline NIHSS score, vascular territory, stroke etiology by TOAST classification, risk factors, rTPA dose, and needle time were documented. RTPA was given at a dose ranging from 0.6mg/kg to 0.9mg/kg. Weight was estimated. The patients received standard stroke care secondary prevention and inhospital rehabilitation following current recommendations. A repeat head CT scan was done 24 hours after thrombolysis, or earlier when there was neurologic deterioration. Hemorrhagic transformation was documented. The mortality rate and other adverse events such as bleeding elsewhere in the body, and orolingual edema were documented. Functional outcome on discharge was dichotomized into 2 groups as follows: Good outcome was defined as MRS score of 0 to 2, while poor outcome was defined as MRS 3 to 6.

No monetary benefits were given to participants of the study. There is no conflict of interest in the use of rTPA. Confidentiality of data and anonymity of patients were ensured. All the data gathered were kept confidential using pseudonyms/codes. The study commenced upon Ethical Review Committee approval. The study was approved by the ethics committee of the institution.

Descriptive statistics for baseline and demographic data are presented. The association of MRS and the age group, baseline NIHSS, stroke etiology, and adverse events are analyzed using the statistical package of social sciences. ANOVA was used as analytical statistics; the alpha level is set at 0.05.

Out of 1939 acute ischemic stroke patients admitted, 110 were potentially eligible. Inclusion criteria are as follows: (1) age > 18 years old (2) clinical diagnosis of ischemic stroke (3) CT or MRI indicating no hemorrhage. Total enumeration was done. Medical records of patients were reviewed. Three (3) were excluded due to the transfer of hospital (2) and incomplete data in the chart (1), finally arriving at a study population of 107 (Figure 1).

Table 1 shows demographics, baseline characteristics, and risk factors for stroke. There were more males (63.55%) and the majority were within 45 to 79 years. The mean age was 58 years, ranging from 20 to 88. 17.75% were stroke in the young and 6.54% were more than 80 years old.

Four patients took Aspirin, 2 patients took Clopidogrel and 2 other patients took RIvaroxaban prior to thrombolysis. The mean systolic BP and diastolic BP was 165/97. Hypertension (82.24%) was the prevalent risk factor, followed by cardiac disease namely CHF and AF (38.31%) then diabetes mellitus (15.88%). The majority of patients (68.22%) had moderate strokes of thrombotic etiology at the MCA territory. Around 13% were infarcts of the posterior circulation. Nine cases (8.41%) were in-hospital strokes and interdepartmental referrals. One of them was managed by the department of neurology as a case of Transient Ischemic Attack who had a stroke while admitted. The other 8 inhospital strokes were managed by the Department of Internal Medicine primarily due to pulmonary disease (6 cases) and Chronic Kidney Disease (2 cases).

Most of the patients (88.79%) received a dose of 0.6mg/kg of rTPA. The average onset of stroke to door time was 74 minutes. The average door to scan time was 33 minutes. Average door to needle time was 94 minutes and average needle time was 149 minutes. The mean length of hospitalization was 9 days with a range of 2 to 42 days.

A favorable outcome on discharge defined as MRS 0 to 2 was achieved by 57%. Of those who had good outcome, half of them had a discharge MRS score of 1. Poor outcome was seen in 42.99% and the majority of them were MRS 3 on discharge. The hemorrhagic conversion was seen in 14.01%, and the majority were asymptomatic. Six patients (5.60%) had symptomatic ICH, of whom all of them died. 4.67% had bleeding outside the CNS which was uncomplicated. 15.88% had malignant infarct of whom half had died due to brain herniation. Eight patients (7.48%) had Basilar Artery Occlusion and 4 of them died Table 2.

Overall Mortality rate during the hospital stay was 15.88% (n=17). In 15 patients, the cause of death was neurologic while 2 deaths were due to medical causes namely fatal arrhythmia and acute respiratory failure. The study investigated the relationship between age group, needle time, stroke severity, stroke etiology, presence of hemorrhagic conversion, and discharge outcome (see Table 3). There was no significance as to age group and needle time. Stroke etiology is a significant factor in discharge outcome revealing cardioembolism as a factor for poor discharge outcome. Severe stroke and sICH are associated factors for poor discharge outcomes.

None of the patients with a needle time of more than 4.5 hours had symptomatic hemorrhage. The average needle time was 327 minutes. Baseline NIHSS ranged from 5 to 26, with a mean NIHSS of 16. Among those with hemorrhagic conversion (see Table 4), most of the patients were males with a mean age of 60 who received rTPA at 0.6mg/kg dose. The mean NIHSS was 15 and the majority had cardioembolic strokes (80%) of the MCA territory. Around 60% had hemorrhagic transformation (HT) while 33% had parenchymal hematoma (PH). Overall, the majority had poor outcomes (60%).

In the subgroup analysis of the mortality cases in the study (see Table 5), the mean age was 60 and most of them were males (64.7%). The majority (64.7%) had a moderate stroke and 29.4% had a severe stroke, with a mean baseline NIHSS of 15. Most (70.59%) had cardioembolic strokes of the right MCA territory (5.9% LMCA territory), 23.5% had basilar artery occlusion, and 18% patients had ICA occlusion. The mean baseline blood pressure was 180/100mmHg. Four patients had comorbidities namely CAP HR, CKD, COPD, and RHD in CHF. The average needle time was 165 minutes, of whom, the majority (16/17) received a dose of 0.6mg/kg. Thrombectomy is not available in the institution. A few patients were able to avail of surgical intervention due to financial difficulties. Of the fifteen (15) mortality cases who had neurologic causes of death, three patients underwent decompressive hemicraniectomy and one underwent tube ventriculostomy.

In general, the results show that acute ischemic stroke patients given rTPA benefit from thrombolysis upon hospital discharge (57%).

Our data indicate favorable discharge outcomes of intravenous thrombolysis administered to stroke patients. A high baseline NIHSS, cardioembolic stroke etiology, and presence of sICH are seen in patients with poor outcome. The rate of sICH is consistent with other literature, however our study has a higher mortality rate for this group. Mortality is high primarily due to malignant infarct (47%), sICH (35%), and BAO (24%).

There is still great room for improvement regarding stroke management, by giving rtpa to more patients and by giving it faster. The study reflects the capacity of the institution and perhaps the capacity of our nation to address acute stroke and thrombolysis complications. Current stroke care is patchy with few centralized areas of excellence unevenly distributed in the country, with majority of its population unable to access it. Additional infrastructure, equipment, and manpower, and stronger interdepartmental and inter-agency coordination is needed and can be strongly addressed in the national level and local government units, and with the collaboration of the public and private sector.

The researcher would like to thank the government higher education center of the Philippines that has facilitated the research and given permission to access the necessary data. The researcher would like to thank all parties who have contributed to this research.

The author conducted the research from the beginning to the end of the study.

No funding has been received to conduct this study.

No data are available for this study.

The authors declare no conflict of interest.